RxPG News : Anti Cancer Drugs

Anti-angiogenics: a novel class of drugs against solid tumors

Thu, 06 Jul 2006 03:03:37 PST

( from http://www.rxpgnews.com ) Researchers at the University of Minnesota have developed novel anti-cancer drugs to treat solid tumors. These "small molecules" belong to a class of pharmaceutical agents called anti-angiogenics. The new compounds are a refined form of drugs that effectively reduce blood flow to the tumor, thereby inhibiting tumor growth. The results of the study appear in the July 5 issue of the Journal of the National Cancer Institute.

"This is a novel class of drugs that increases the potential for good, effective treatment for cancer patients with tumors," said Kevin Mayo, Ph.D., principle investigator and professor of biochemistry, molecular biology and biophysics at the University of Minnesota Medical School.

There is currently a protein anti-angiogenic agent approved by the FDA for clinical use. These new tumor-targeting compounds were designed to mimic the functional part of an anti-angiogenic protein. But, because the compounds are not proteins themselves, they have the advantage of possibly being taken in pill form and being less costly to produce.

In animal studies with mice, the compounds inhibited tumor growth by up to 80 percent, and in combination with chemotherapy tumors essentially disappeared. Although the compounds proved effective against solid tumors, researchers believe they have potential to treat liquid tumors as well, such as the type found in leukemia and other blood cancers.

"Our next step is to treat people with the drug in FDA-approved clinical trials," said Mayo.

Rituximab effective in treating chronic graft-versus-host disease

Fri, 24 Mar 2006 19:14:37 PST

( from http://www.rxpgnews.com ) A study by Dana-Farber Cancer Institute researchers offers the strongest evidence yet of the effectiveness of a novel therapy for chronic graft-versus-host disease (GVHD), a potentially life-threatening complication of donor bone marrow and stem cell transplants.

The use of the therapy, a drug known as rituximab, grew out of recent discoveries about the human immune system and the interactions between transplanted cells and recipients' own tissue. In the new study, posted on the website of the journal Blood, researchers found that rituximab reduced the severity of chronic GVHD in 70 percent of the study participants who completed at least one course of treatment, including two who experienced complete remissions of symptoms. The benefits, which continued up to a year after therapy, occurred mainly in patients whose skin and musculoskeletal systems were affected by chronic GVHD.

"Our findings validate the preliminary work about the benefits of rituximab for this group of patients," says the study's lead author, Corey Cutler, MD, MPH, of Dana-Farber. "It offers a new line of therapy for individuals for whom, until now, few good options have existed."

Chronic graft-versus-host disease is the most common cause of disease and death among long-term survivors of donor stem-cell transplants for certain forms of cancer and blood diseases, affecting 60-70 percent of long-term survivors. It occurs when immune system cells in transplanted tissue launch an attack on recipients' own tissue, producing problems that can range from a mild rash to diarrhea and fever to life-threatening disorders. Despite therapy that can last months or years, chronic GVHD kills up to a third of all those who survive long-term after stem-cell transplants for leukemia.

Traditionally, scientists have thought that GVHD is caused by T cells, immune system cells whose job is to attack foreign tissue and which enter transplant recipients along with donor stem cells. This thinking has been challenged by research, by Dana-Farber's Jerome Ritz, MD, and others, that indicates that immune system B cells, as well as T cells, play a critical role in GVHD. (T cells are so named because they mature in the thymus gland, while B cells are derived from bone marrow.) This hypothesis gained traction when laboratory studies and small clinical trials showed that rituximab, which specifically targets B cells, could be effective against GVHD.

The new study reinforces those findings with the largest group of chronic GVHD patients yet treated with rituximab. The patients in the study had chronic GVHD that was resistant to the standard therapy of corticosteroids, and were on stable doses of other immune system-suppressing medications. Twenty of the study's 21 participants completed at least one 4-week course of treatment. All had received stem cell transplants at least six months before enrolling in the study.

In addition to reducing the severity of GVHD in nearly three-fourths of the study participants, rituximab enabled 68 percent of the participants to reduce the amount of corticosteroids they were taking by more than 50 percent. Patients reported few side effects of the rituximab therapy.

"We've demonstrated that anti-B cell therapy with rituximab is safe and effective for patients with steroid-resistant chronic GVHD," Cutler says. "It's becoming clearer that treatments for chronic GVHD will need to take account of both T cell and B cell activity in transplant recipients. The success of this approach suggests that anti-B cell therapies cold be tested as part of a strategy for preventing GVHD and treating it in its earliest stages."

Tarvacin(TM) Anti-Viral Hepatitis C Clinical Program in Acceleration Phase

Wed, 18 Jan 2006 18:00:37 PST

( from http://www.rxpgnews.com ) Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a biopharmaceutical company with a portfolio of innovative, clinical-stage product candidates for viral diseases and cancer, today announced that it has accelerated its clinical program for Tarvacin(TM) Anti-Viral for the treatment of chronic hepatitis C virus infection (HCV).

As a result of rapid enrollment in the Phase I HCV study, Peregrine is now targeting completion of patient dosing in February, several months ahead of initial estimates. Top-line safety data from the study will be presented by the company at the Viral Hepatitis in Drug Discovery and Development Meeting to be held in Boston on February 27, 2006. Tarvacin is also in a Phase I cancer trial for patients with advanced refractory solid tumors.

"The initial success of our efforts to accelerate the HCV clinical trial program for Tarvacin Anti-Viral is gratifying in view of Tarvacin's promise as an important new treatment option for a number of viral infections, including chronic hepatitis C infection," said Steven W. King, president and CEO of Peregrine. "In anticipation of completing the Phase I study ahead of schedule, we are now initiating additional collaborations with leading researchers and institutions in the HCV field to advance Tarvacin Anti-Viral to the next phase of development."

In the Phase I trial, a single dose of Tarvacin is being tested in patients with chronic hepatitis C infection. Data from the current study will enable the company to make preliminary assessments of Tarvacin's safety, drug distribution and clearance rates. Since patients with hepatitis C infection are being treated in this study, rather than healthy volunteers, data collected from the trial will be particularly relevant in designing repeat dose and combination therapy clinical trials that are expected to begin later this year. These additional studies will allow more complete assessments of the product's therapeutic potential.

Tarvacin is a monoclonal antibody with unique anti-viral properties. It attaches to specific cellular components called phospholipids found on the surface of virus particles, including influenza and certain other virus strains, as well as on the outer surface of human host cells only when they are infected with these viruses. Tarvacin helps stimulate the body's natural immune defenses to destroy both the virus particles and the infected cells. Since the targeted phospholipids are not exposed on healthy cells, they are not affected by Tarvacin, which in studies to date appears to be safe and well tolerated. Tarvacin Anti-Viral is also in preclinical studies for potential use against influenza, HIV, cytomegalovirus and other life-threatening viruses.

Similar to its anti-viral mechanism, Tarvacin also binds to phospholipids exposed on tumor blood vessels in all solid cancers tested to date, and it has shown promise in a number of preclinical cancer studies. Tarvacin Anti-Cancer is currently in a multi-center Phase I clinical trial for patients with advanced refractory solid tumors.

Tarvacin effective in controlling Pancreatic Cancer

Wed, 11 Jan 2006 19:20:37 PST

( from http://www.rxpgnews.com ) Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a biopharmaceutical company with a portfolio of innovative, clinical-stage product candidates for viral diseases and cancer, today announced preclinical results showing that 3G4, the mouse equivalent of Tarvacin(TM) Anti-Cancer, was effective at controlling the growth and spread of pancreatic cancer as a single agent and had significantly enhanced efficacy when combined with the standard-of-care chemotherapy gemcitabine. Pancreatic cancer is very difficult to treat and has the lowest 5-year survival rate of all malignancies. In this study, the Tarvacin equivalent antibody demonstrated promising activity against the primary tumor itself as well as the metastases that actually cause most pancreatic cancer deaths. The study will be published in the International Journal of Cancer (volume 118, edition 10) and is currently available online (published online: 13 Dec 2005, DOI: 10.1002/ijc.21684.)

Tarvacin Anti-Cancer is in a multi-center Phase l trial for solid tumor cancers. It is a monoclonal antibody that binds to certain phospholipids, components of the cell structure that are usually located inside normal cells but which become exposed on the outside of the cells that line the blood vessels of tumors, creating a specific target for anti-cancer treatments. This study compared the Tarvacin equivalent antibody and gemcitabine as single agents and in combination in two realistic and clinically relevant mouse models of pancreatic cancer.

The Tarvacin equivalent antibody and gemcitabine each reduced the tumor and metastatic burden in these mice, but combination therapy with the two agents was significantly more effective than either agent alone. Combination therapy reduced primary tumor burden by 60% in both models. Furthermore, combination therapy reduced metastatic events by 80% at each of the principal sites of pancreatic metastasis and significantly reduced the number of mice with liver metastases in both models. This is of clinical importance since the liver is the major site of blood-born metastases in pancreatic cancer, and metastatic liver tumors are the most common source of therapeutic failure in patients after surgical removal of the primary tumor.

"We are very encouraged by the results of this study and eager for the opportunity to study Tarvacin Anti-Cancer in pancreatic cancer patients," said Rolf Brekken, Ph.D., a cancer researcher at the University of Texas Southwestern Medical Center and senior author of the study. "While Tarvacin shows promising activity as a single anti-cancer agent, these study results suggest that the combination of Tarvacin with chemotherapy amplifies and increases the exposure of Tarvacin's target on the surface of the tumor blood vessels, creating an additive therapeutic effect with no discernable increase in toxicity of the chemotherapeutic agent."

Researchers at UT Southwestern Medical Center and Peregrine are collaborating on plans for a trial of Tarvacin Anti-Cancer in pancreatic cancer after completion of Peregrine's current Phase I cancer study.

"We now have a growing body of evidence demonstrating that Tarvacin Anti- Cancer has broad therapeutic potential against both primary tumors and tumor metastases in several major cancers, including cancers of the prostate, breast and pancreas," said Steven W. King, president and CEO of Peregrine. "Given its consistent record of promising efficacy in these preclinical studies, we plan to pursue multiple clinical trials for Tarvacin Anti-Cancer after we successfully complete the Phase l study now underway."

Similar to its mechanism of action in cancer, Tarvacin targets phospholipids exposed on viruses and virally infected cells, mobilizing the immune system to attack and destroy both the viruses and the infected cells. Tarvacin Anti-Viral is in Phase I clinical studies for hepatitis C infections and is in pre-clinical studies for potential use against influenza, HIV, cytomegolous virus and other life-threatening viruses.

The study, Combination of a monoclonal anti-phosphatidylserine antibody with gemcitabine strongly inhibits the growth and metastasis of orthotopic pancreatic tumors in mice, by Adam W. Beck, Troy A. Luster, Andrew F. Miller, Shane E. Holloway, Chris R. Conner, Carlton C. Barnett, Philip E. Thorpe, Jason B. Fleming and Rolf A. Brekken, was funded with grants from the National Institutes of Health, National Pancreas Foundation, American Cancer Society, Effie Marie Cain Scholarship in Angiogenesis Research and The Gillson Longenbaugh Foundation.

Rituximab maintenance therapy dramatically improves survival in lymphoma

Tue, 13 Dec 2005 15:35:38 PST

( from http://www.rxpgnews.com ) Two years of maintenance therapy with MabThera (rituximab) dramatically improves the chances of survival for patients suffering from one of the most frequent forms of lymphoma, indolent non-Hodgkins Lymphoma (NHL). The trial showed that the risk of death is halved for patients who receive MabThera maintenance therapy, compared to those who receive no maintenance treatment, irrespective of their initial therapy. We are conscious that these results open a new era in the management of indolent NHL, said William M. Burns, CEO of the Pharmaceuticals Division at Roche. Maintenance therapy with MabThera showed unprecedented survival benefits in a serious cancer disease which is currently considered incurable.

Professor Marinus van Oers M.D. from the Academic Medical Center of the University of Amsterdam and lead investigator of the pivotal study said: Our trial confirms that MabThera maintenance therapy is highly beneficial for all patients, including those who have already received MabThera as part of their initial therapy. Maintenance therapy with MabThera may well become the new standard of care for these patients.

In the EORTC 20981 (European Organisation for Research and Treatment of Cancer) trial, 465 patients with relapsed and refractory indolent NHL were randomised to receive either 3-weekly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy or MabThera plus CHOP as induction therapy. Responding patients were then again randomised to either MabThera maintenance, or observation (no further treatment).

The primary endpoints were response rates and progression-free survival for the initial treatment phase and the maintenance phase of the study, respectively. The trial was performed in 130 centres in Canada, Australia, Netherlands, UK, Norway, Slovenia, Slovakia, Belgium, Hungary, South Africa, Sweden, New Zealand, Denmark, Egypt, France, Switzerland, Italy and Poland.

The results of the induction phase of the trial showed that patients who received MabThera and CHOP (R-CHOP) had a significantly higher rate of complete remission than patients who received CHOP chemotherapy alone (29% vs 16%, p value <0

Peregrine Pharmaceuticals Evaluating Therapeutic Opportunities for Tarvacin

Tue, 25 Oct 2005 05:10:38 PST

( from http://www.rxpgnews.com ) Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM) at its Annual Meeting of Stockholders today will provide a review of its ongoing programs to evaluate its unique anti-phospholipid agent Tarvacin(TM) Anti-Viral for the treatment of influenza. Peregrine is actively collaborating with the National Institutes of Allergy and Infectious Diseases (NIAID) to assess Tarvacin Anti-Viral in preclinical flu models, and the company is also working directly with academic research centers and private research organizations to evaluate Tarvacin as a stand-alone agent and in combination with existing influenza therapies. In addition, Peregrine has entered into discussions with other federal officials to evaluate the potential of Tarvacin to treat influenza, including avian flu. Tarvacin Anti-Viral is currently in a Phase I clinical trial for the treatment of chronic hepatitis C virus infections.

Tarvacin is a monoclonal antibody that attaches to phospholipids, specific cellular components that are exposed on the outer surface of all enveloped viruses tested to date including influenza, as well as on the human host cells that are infected with these viruses. Enveloped viruses, which have a coating derived from their host's cell membrane, are responsible for about half of all human viral diseases. Tarvacin Anti-Viral has been shown to protect animals from lethal infections in two preclinical models of enveloped viruses -- cytomegalovirus and pichinde virus, a model for the deadly Lassa hemorrhagic fever. Peregrine has previously reported that Tarvacin Anti-Viral binds to members of six different virus families, including influenza A and B, HIV 1 and 2, measles, respiratory syncytial virus and pichinde virus. Recent studies confirmed that Tarvacin Anti-Viral binds to human cells infected with influenza A.

"Evaluating Tarvacin Anti-Viral as a potential treatment for influenza, including deadly new strains such as avian flu, is a high priority for the company," said Steven King, president and CEO of Peregrine. "Given current global concerns about the possibility of an avian flu pandemic, we are rapidly identifying and assessing a number of opportunities to ramp up our existing collaborations with public and private sector partners to further accelerate these studies."

The specific phospholipids targeted by Tarvacin Anti-Viral come from the human host and are incorporated into the envelop the virus acquires as it leaves the host's cells to propagate and spread the viral infection. Unlike drugs that target an attribute of the virus, Tarvacin's host-derived phospholipid target is expected to be less susceptible to the development of drug resistance, since the virus cannot simply mutate to avoid Tarvacin's anti-viral effects.

"The unique mechanism of action and stable nature of the target could make Tarvacin Anti-Viral a particularly attractive clinical candidate for the treatment of influenza, either as a stand-alone agent or in combination with existing therapies," said Joseph Shan, senior director of clinical and regulatory affairs at Peregrine. "We are accelerating our joint efforts with a number of public and private organizations to more fully evaluate the anti-influenza potential of Tarvacin Anti-Viral. If these preclinical studies produce positive results, we plan to expand our activities to expedite the initiation of human clinical trials."

Tarvacin also binds to phospholipids exposed on tumor blood vessels in all solid cancers tested to date, and it has shown promise in a number of preclinical cancer studies. Tarvacin Anti-Cancer is currently in a multi-center Phase I clinical trial for patients with advanced refractory solid tumors.

Balancing Chk1 activity might produce less toxic cancer drugs

Sun, 04 Sep 2005 08:32:38 PST

( from http://www.rxpgnews.com ) A study published by The Burnham Institute in the September edition of Molecular Cell reports that a cell-cycle checkpoint protein, known to be activated by an important class of anticancer drugs, may play crucial roles in both the hampering of therapeutic actions and aiding cancer cells to "recover" and start dividing again after treatment with these drugs. The study is expected to help academic researchers and biotechnology and pharmaceutical companies design drugs that combat cancer using this checkpoint protein, but with fewer side effects.

Robert Abraham, Ph.D., former director of The Burnham Institute's Cancer Center and now vice president for oncology research at Wyeth Pharmaceuticals, together with his colleagues, found that the Chk1 protein responds with cell-survival activity to stressful conditions induced by hypoxia and certain anticancer drugs. Furthermore these same conditions target Chk1 for eventual destruction. Ironically, stimulation of Chk1 triggers certain repair responses that fight cancer while the simultaneous degradation of Chk1 can allow cancer cells to escape drug-induced death and resume progressive tumor growth.

The study suggests the Chk1 protein is critical for ensuring the repair of mutations and other errors in DNA replication before they can alter the function of a cell. If not repaired, these errors can kill the cell when it attempts to divide and proliferate. In cancer cells, Chk1 is responds as a natural defense to the therapeutic damage done by radiation and chemotherapy and attempts to effect repair to DNA damage caused by the cancer therapy, thus makes the drug therapy less effective.

The researchers also found that the chemotherapy agent campthothecin (CPT), a clinically important anticancer agent, reduced the activity of the Chk1 protein. "These findings lend strong support to the idea that inactivation of Chk1 contributes to the antitumor activity of CPT by allowing cells bearing damaged DNA to progress through the cell cycle, leading to an unsuccessful and often lethal attempt to undergo cell division," said Abraham. "Combination therapy, which pairs a chemotherapy agent with an inhibitor of Chk1, may therefore be an effective strategy to increase the efficacy of certain anticancer drugs, and may well overcome clinical resistance to these drugs."

By studying the effects of radiation and other stresses on the pathway that normally regulate Chk1, the researchers discovered that the same pathway that activates Chk1 via phosphorylation by its regulatory enzyme, ATR, also marks Chk1 for eventual destruction.

"We expect this process prevents activated Chk1 from accumulating in normal cells and prevents abnormal cell proliferation," said Abraham. "ATR activates, but also destabilizes Chk1, which creates a homeostatic mechanism that balances the genome protective function of Chk1 with the process of cell proliferation. This is a new look at drug therapy. Textbook descriptions of ATR and Chk1 don't describe this dual role."

"The findings also provide further insight into Chk1 activation and tumor sensitivity," Abraham added. "Cancer cells rely heavily on Chk1 for survival and proliferation under stressful environmental conditions. Instead of halting abnormal growth of cancer cells, drug therapy could in effect induce Chk1 natural activity to prevent cell death in cancer cells."

Rituximab to be Considered for Front-Line Treatment of Intermediate Grade or Aggressive CD-20-positive, B-cell, non-Hodgkin's lymphoma

Thu, 18 Aug 2005 11:44:38 PST

( from http://www.rxpgnews.com ) Genentech, Inc. , Biogen Idec, Inc. and Roche (SWX Zurich) today announced that the companies completed the filing of a supplemental Biologics License Application (sBLA) with the U.S. Food and Drug Administration (FDA) for an additional indication for Rituxan(R) (Rituximab), in previously untreated (front-line) patients with intermediate grade or aggressive, CD-20-positive, B-cell, non-Hodgkin's lymphoma (NHL) in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens. As part of the Rituxan sBLA filing, the companies have requested Priority Review designation from the FDA. Rituxan is currently approved for use in relapsed or refractory, low-grade or follicular, CD-20-positive, B-cell, non-Hodgkin's lymphoma.

The sBLA filing is based on efficacy and safety data from three randomized, controlled, multicenter studies of Rituxan in combination with CHOP or other anthracycline-based chemotherapy induction regimens in 1,854 previously untreated patients with intermediate grade or aggressive, CD-20-positive, B-cell, non-Hodgkin's lymphoma. All three trials evaluated the efficacy endpoint of overall survival.

"These three Phase III studies add to the body of data regarding Rituxan in the treatment of non-Hodgkin's lymphoma," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer. "We are pleased to be filing these data with the FDA, and we are committed to working closely with the agency during the review process."

"The addition of Rituxan to CHOP represents the first significant improvement in intermediate grade or aggressive CD-20-positive, B-cell NHL treatment since the development of the CHOP regimen more than 30 years ago," said Burt Adelman, M.D., Biogen Idec's executive vice president, Development.

The studies included in this filing are ECOG 4494 (a National Cancer Institute-sponsored intergroup trial led by the Eastern Cooperative Oncology Group), GELA/LNH 98-5 (the Group d'Etude des Lymphome d'Adulte) and MInT (MabThera International Trial M39045).

Study E4494 was designed to evaluate the efficacy and safety of Rituxan combined with induction CHOP chemotherapy in 632 patients 60 years of age or older with intermediate-grade or aggressive, CD-20-positive, B-cell, NHL.

The LNH 98-5 trial conducted by GELA was designed to evaluate the efficacy and safety of Rituxan in combination with induction CHOP chemotherapy in 399 patients 60 years of age or older with Diffuse Large B-Cell Lymphoma (DLBCL). Based on the results of this trial, in March 2002, Rituxan, which is known as MabThera(R) in Europe received approval from the European Union health authority to treat aggressive NHL.

The M39045 (MInT) trial was designed to evaluate the efficacy and safety of Rituxan in combination with CHOP or other anthracycline-based induction chemotherapy regimens in 823 patients between the ages of 18-60.

About Non-Hodgkin's Lymphoma

There are currently more than 360,000 people in the United States living with NHL. Approximately 50 percent have aggressive NHL, while the other half are patients with indolent or follicular lymphoma. According to the American Cancer Society, more than 56,000 men and women in the United States are diagnosed with NHL each year.

Rituxan Safety Profile

Rituxan is generally well tolerated by patients. The majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include but are not limited to: flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and generally are reversible with medical intervention. In rare instances, severe and fatal infusion-related reactions have occurred, nearly all of which have been associated with the first Rituxan infusion. These events appear as manifestations of an infusion-related complex and include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock and tumor lysis syndrome. Patients who develop clinically significant infusion-related cardiopulmonary events should have their Rituxan infusion discontinued and receive medical treatment.

In rare instances, severe mucocutaneous skin reactions have occurred that may be associated with Rituxan therapy. Many of these reactions have been described as paraneoplastic pemphigus and are known to be associated with various B-cell lymphomas, particularly NHL and chronic lymphocytic leukemia (CLL). Patients who develop a severe mucocutaneous skin reaction should have Rituxan discontinued and receive appropriate medical treatment including a skin biopsy to guide therapy.

About Rituxan

Rituxan received U.S. Food and Drug Administration approval in November 1997 for the treatment of relapsed or refractory low-grade or follicular, CD-20-positive, B-cell, non-Hodgkin's lymphoma (NHL). It also was approved in the European Union under the trade name MabThera(R) in June 1998. Rituxan has been used to treat more than 730,000 patients worldwide.

Rituxan is a therapeutic antibody that targets and selectively depletes CD-20-positive, B-cells without targeting stem cells or existing plasma cells. In April 2005, the companies announced positive findings from a Phase III study evaluating the safety and efficacy of Rituxan in patients with active rheumatoid arthritis (RA) who had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies. Rituxan is also being investigated in other autoimmune diseases, including lupus, multiple sclerosis and ANCA-associated vasculitis.

Tarvacin(TM) starts with Phase I study against Hepatitis C Virus

Mon, 08 Aug 2005 17:39:38 PST

( from http://www.rxpgnews.com ) Enrollment Open for Patients Chronically Infected With Hepatitis C Virus (HCV)

Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), announced today the initiation of a phase I anti-viral study of Tarvacin(TM), the Company's first Anti-Phospholipid Therapy candidate. The phase I study is an open-label, dose-escalation study in up to 32 adult patients with chronic hepatitis C virus (HCV) infection who either no longer respond to or failed standard therapy with pegylated interferon and ribavirin combination therapy.

The objectives of the trial are to evaluate safety, pharmacokinetics and viral load following a single intravenous infusion. The study is being conducted at Bach and Godofsky Infectious Diseases, the largest private infectious disease practice specializing in the treatment of viral hepatitis in the United States. Bach & Godofsky is located in Bradenton, FL.

"Tarvacin(TM) is truly a novel approach to treating HCV and we are eager to offer patients the opportunity to participate in this trial," stated Eliot W. Godofsky, M.D., Principal Investigator and clinical assistant professor of medicine at the University of South Florida in Tampa.

"This study is an important step for our Tarvacin(TM) antiviral program," said Joseph Shan, Peregrine's senior director of clinical and regulatory affairs. "Meanwhile, we are continuing our Tarvacin(TM) development efforts for other viral diseases."

New data support broad anti-viral potential of Tarvacin(TM)

Sun, 31 Jul 2005 23:59:38 PST

( from http://www.rxpgnews.com ) Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), has presented new data at the Biotechnology Industry Organization 2005 (BIO 2005) annual meeting in Philadelphia, PA. supporting the broad anti-viral potential of Tarvacin(TM). The data presented at BIO 2005 showed that Tarvacin(TM) binds to enveloped virus particles representing 6 different virus families, binds to virally infected cells and inhibits viral replication in multiple virus systems. The data also indicated that Tarvacin(TM) provided significant protection against Cytomegalovirus (CMV) and Pichinde virus (an in vivo Lassa fever model) infections.

Data presented at the conference demonstrated:

Tarvacin(TM) binds to viruses from six different enveloped virus families, including specific binding to HIV 1 and 2, Influenza A and B, Measles, Respiratory Syncitial Virus (RSV), Bovine Viral Diarrhea (a surrogate in vitro Hepatitis C virus model), and Pichinde virus.
Tarvacin(TM) binds to cells infected with Influenza, Vaccinia (a model for Smallpox) and Pichinde viruses.
Anti-Phosphatidylserine antibodies inhibited replication of RSV, Vesicular Stomatitis Virus and Pichinde viruses.
Anti-Phosphatidylserine antibodies provided significant protection in animals infected with cytomegalovirus (CMV) with 100% of the Anti- Phosphatidylserine antibodies treated animals surviving and only 20% of animals receiving control treatment surviving.

Tarvacin(TM) provided significant protection in animals administered lethal viral loads of Pichinde virus (a model of Lassa fever) with 50% of the Tarvacin(TM) treated animals surviving and none of the animals receiving control treatment surviving.

Animals lethally infected with Pichinde virus that survived following Tarvacin(TM) therapy had long term immunity to reinfection.

"These data further illustrate why we are excited about the Tarvacin(TM) anti-viral program," stated Steven King, president and CEO of Peregrine. "We are looking forward to initiating the Tarvacin(TM) Hepatitis C clinical trial, continuing our collaboration with National Institute of Allergy and Infectious Diseases (NIAID) and expanding into other collaborations to further explore the potential of the program for the treatment of viral infections."

Peregrine received FDA approval to begin a Tarvacin(TM) phase I clinical trial in Hepatitis C infected patients in late May 2005. In April of 2005, Peregrine and the National Institute of Allergy and Infectious Diseases (NIAID) entered into a collaborative effort to screen Tarvacin(TM) for activity both in vitro and in vivo against a wide variety of enveloped viruses of health and bioterrorism concern including Hepatitis C, influenza and SARS. Peregrine is continuing to evaluate Tarvacin(TM) for the treatment of a variety of viral infections that could lead to additional therapeutic indications in this area. In addition, Peregrine is currently recruiting patients in a Tarvacin(TM) phase I clinical trial that is open to patients with advanced solid tumor cancer.

About Tarvacin(TM)

Anti-Phospholipid Therapy is Peregrine's novel approach to treating cancer, viral infections and certain other diseases. It is based on the finding that aminophospholipids, which are basic components of the inner surface of the cellular membrane, become exposed in certain disease states. Tarvacin(TM) is a chimeric monoclonal antibody that binds to the phospholipid, phosphatidylserine, and is part of Peregrine's Anti-Phospholipid Therapy platform. Tarvacin(TM) binds directly to tumor blood vessels to inhibit growth and development of solid tumors. Tarvacin(TM) has also shown promise in the treatment of viral infections and is expected to recognize a broad spectrum of enveloped viral types. Tarvacin(TM) is currently being evaluated for the treatment of both cancer and viral diseases. Peregrine has received FDA approval to initiate two separate Phase 1 clinical trials in advanced solid cancer and chronic Hepatitis C virus indications.

About Enveloped Viruses

A large number of viruses significant to global health and security possess an "envelope" derived from their host cell membrane. The outer shell of the virus is known as the viral envelope. Since viruses lack the means to maintain structural organization of the envelope, amino-phospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) become exposed on the surface of these viruses, making them a potential therapeutic target. Peregrine Pharmaceuticals, together with its collaborators, has developed a series of monoclonal antibodies, including Tarvacin(TM), directed against aminophospholipids to take advantage of this property.

Tarvacin(TM) also useful in imaging solid tumors

Sun, 31 Jul 2005 23:12:38 PST

( from http://www.rxpgnews.com ) Peregrine Pharmaceuticals, Inc reported that data was presented at the American Association for Cancer Research (AACR) Annual Meeting in Anaheim, California showing the potential use of Tarvacin(TM), its lead Anti-Phospholipid Therapy agent, for imaging solid tumors. The presentation talk was titled "Tumor Imaging With The Vascular Targeting Antibody Tarvacin(TM) Labeled with Arsenic Isotopes".

Data presented showed that Tarvacin(TM) could be used to deliver a radioactive arsenic compound to prostate cancer blood vessels for tumor imaging. An earlier presentation at the AACR Annual Meeting had shown the potential of Tarvacin(TM) for the treatment of prostate cancer. Peregrine expects to begin patient enrollment in a Tarvacin(TM) phase I clinical trial for the treatment of cancer within the next 30 days.

"These imaging data indicate another potential utility for Tarvacin(TM) and other agents that fall under our Anti-Phospholipid Therapy technology platform," said Steven King, president and CEO of Peregrine Pharmaceuticals. "We will continue to explore additional ways to fully utilize this technology platform for the treatment and therapy of cancer and other diseases. In addition to its anti-cancer activity, the company recently announced data showing Tarvacin's impressive anti-viral activity and the company has been evaluating the compound for activity in treating ocular disease."

Tarvacin(TM) to be evaluated for the treatment of Lassa fever

Sun, 31 Jul 2005 23:01:38 PST

( from http://www.rxpgnews.com ) Peregrine Pharmaceuticals Inc. has announced that it has signed a Cooperative Research and Development Agreement (CRADA) for Material Transfer with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) to evaluate the potential therapeutic application of Tarvacin(TM) to treat hemorrhagic diseases resulting from Ebola and Marburg viral infections. Under the agreement, Peregrine will supply Tarvacin(TM), its lead anti-phospholipid therapy agent, for in vitro and in vivo animal studies developed by the USAMRIID under the direction of Thomas W. Geisbert, M.D., Chief, Department of Viral Pathology and Ultrastructure at USAMRIID, Fort Detrick, MD.

"We are very pleased to be able to work with the group at USAMRIID to further explore possible anti-viral biodefense applications of Tarvacin(TM)," said David Sherris, Ph.D., Peregrine's head of business development. "This agreement will allow us to expand on the promising results previously generated using Tarvacin(R) to treat a model of another hemorrhagic fever known as Lasssa fever."

Recent data presented at the Biotechnology Industry Organization 2005 annual meeting in Philadelphia, Pennsylvania showed that Tarvacin(TM) binds to enveloped virus particles representing 6 different virus families and binds to virally infected cells. The data also showed that Tarvacin(TM) provided significant protection against Cytomegalovirus (CMV) and Pichinde virus (an in vivo Lassa fever model) infections. In April of 2005, Peregrine and the National Institute of Allergy and Infectious Diseases (NIAID) entered into a collaborative effort to screen Tarvacin(TM) for activity both in vitro and in vivo against a variety of enveloped viruses of health and bioterrorism concern including Hepatitis B and C, HIV, influenza and SARS.

Peregrine received FDA approval to begin a Tarvacin(TM) Phase I clinical trial in Hepatitis C infected patients in late May 2005. Peregrine is continuing to evaluate Tarvacin(TM) for the treatment of a variety of viral infections that could lead to additional therapeutic indications in this area. In addition, Peregrine is currently recruiting cancer patients in a Tarvacin(TM) Phase I clinical trial at multiple clinical sites in the United States.

About Tarvacin(TM)

Anti-Phospholipid Therapy is Peregrine's novel approach to treating cancer, viral infections and certain other diseases. It is based on the finding that aminophospholipids, which are basic components of the inner surface of the cellular membrane, become exposed in certain disease states. Tarvacin(TM) is a chimeric monoclonal antibody that binds to the phospholipid, phosphatidylserine and is part of Peregrine's Anti-Phospholipid Therapy platform. Tarvacin(TM) binds directly to tumor blood vessels to inhibit growth and development of solid tumors. Tarvacin(TM) has also shown promise in the treatment of viral infections and is expected to recognize a broad spectrum of enveloped viral types. Tarvacin(TM) is currently being evaluated for the treatment of both cancer and viral diseases. Peregrine has received FDA approval to initiate two separate Phase 1 clinical trials in advanced solid cancer and chronic Hepatitis C virus indications.

About Enveloped Viruses

A large number of viruses significant to global health and security possess an "envelope" derived from their host cell membrane. The outer shell of the virus is known as the viral envelope. Since viruses lack the means to maintain structural organization of the envelope, amino-phospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) become exposed on the surface of these viruses, making them a potential therapeutic target. Peregrine Pharmaceuticals, together with its collaborators, has developed a series of monoclonal antibodies, including Tarvacin(TM), directed against aminophospholipids to take advantage of this property.

DANCER Study shows RA drug rituximab is safe and well-tolerated

Thu, 09 Jun 2005 13:25:38 PST

( from http://www.rxpgnews.com ) In the biggest study of its kind, researchers have shown that the drug rituximab, used to treat rheumatoid arthritis (RA) is safe and effective. The results were presented for the first time today (Thursday 9 June), at the Annual European Congress of Rheumatology, EULAR 2005, in Vienna.

Professor Paul Emery from the University of Leeds in the UK led the DANCER study (Double blind placebo controlled dose ranging study), designed to confirm the efficacy of rituximab for the treatment of patients with active RA who have failed to improve on one or more disease modifying anti-rheumatic drugs (DMARDs). Rituximab targets a specific type of immune cell and helps to control inflammation and pain.

The DANCER study involved 465 men and women who had had arthritis for about 10 years. It examined the relative efficacy of two different dose levels of rituximab, as well as the role of anti-inflammatory drugs, glucocorticoids (steroids), in the treatment programme.

Speaking at the Vienna congress, Professor Emery said, "The results of the study's 24 week-analysis showed that both doses of rituximab were highly effective, and significantly better than a placebo. It seems that that the higher of the two doses produced the best effects."

An intravenous infusion of glucocorticoids alone before the treatment began was compared with a pre-infusion plus a short oral course. Either way, the steroids did not enhance the efficacy of rituximab. "Our analyses demonstrate that rituximab is safe and well-tolerated, consistent with that seen previously in studies of rituximab, in patients with RA," Professor Emery said.

Rituximab may also benefit people with lupus

Thu, 09 Jun 2005 13:25:38 PST

( from http://www.rxpgnews.com ) A drug used to treat cancer may also benefit people with lupus who have complications of the central nervous system. Rheumatologists at the Annual European Congress of Rheumatology in Vienna, Austria heard today (Thursday 9 June) that rituximab is the first drug in a quarter of a century that is making a real impact, and an alternative to previous standard treatments of high-dose steroids, and chemotherapy.

Lupus is a disorder of the immune system in which the body attacks itself, causing pain, inflammation and diffuse damage to many organs. In a significant number of cases, the central nervous system is effected which can lead to psychiatric and neurological disturbances. This form of lupus dramatically reduces the quality of life for patients, more so than other manifestations of the disease in which, for example, the kidneys might be affected.

Clinical professor Michael Neuwelt, at the University of Californian San Francisco and Stanford University, presented results of a trial involving 22 patients over 16 months. "I spent considerable time with oncologists and saw how the drug works in patients with non-Hodgkins lymphoma. Patients with blood disorders of lupus and severe complications of the central nervous system (CNS) also surprisingly improved," he said.

Over half of the patients received rituximab on its own, others received it in combination with steroids, and one-third with the current standard treatment of severe CNS lupus with chemotherapy, cyclophosphamide, combined with rituximab. Rituximab targets a specific type of white blood cells (B cells which make auto-antibodies) and uniquely removes those early B cells before they become harmful. "Rituximab appears to be quite effective. It is a kinder, gentler form of treatment lasting up to six months with a low risk of side-effects, compared to previous treatments of high-dose steroids, and chemo-therapy," said Professor Neuwelt.

There was a significant improvement in 16 of the patients and four others were stabilized. Brain scans demonstrated that the adverse changes that occurred with the disease improved.

Professor Neuwelt specialises in diagnosing and treating patients with CNS lupus. "It can be difficult to disentangle psychiatric disorders that arise from other causes," he states. In a portion of patients, depression, seizures, verbal comprehension, perception and memory will be associated with lupus. People are understandably afraid to admit that their IQ has gone down or that they cannot read any more in fear of losing their job," he continued. A careful history, ruling out other causes such as infection and drug side effects has improved diagnostic accuracy.

Professor Neuwelt, like others using this well-tested oncological drug in other forms of lupus, is concerned about the depletion of the B cells by rituximab for the long term. However, the risk/benefit ratio from this new treatment in its early stages is extremely promising. "It is the first drug in my 26 years of treating patients with severe central nervous system lupus, used alone or in combination with other therapies that has not only significantly boosted the quality of life for patients with this dreadful disease, but also reduced the burden of side effects of standard treatment with steroids and cyclophosphamide. However, we desperately need randomized-controlled trials." he concluded.

PXD101: A Small Molecule HDAC Inhibitor for Advanced Solid Tumors

Tue, 17 May 2005 08:42:38 PST

( from http://www.rxpgnews.com ) CuraGen Corporation (Nasdaq: CRGN - News) and TopoTarget A/S announced that preliminary Phase I data on PXD101, a small molecule histone deacetylase (HDAC) inhibitor, for the treatment of advanced solid tumors were presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida.

This Phase I open-label study was designed to determine the safety, maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of intravenously administered PXD101, as well as initial assessment of the pharmacokinetics of orally administered PXD101.

PXD101 was administered as a single agent to patients with advanced solid tumors whose disease was refractory to standard therapy or for whom no standard therapy existed.

Preliminary data reported on 28 patients receiving PXD101 suggests that this compound is well-tolerated following intravenous and oral administration.

The most common adverse events were fatigue, nausea, vomiting and phlebitis. No hematological toxicities were noted. Clinical investigators described toxicities as mild with no grade 4 toxicity observed.

Histone hyperacteylation, a biomarker of the activity of PXD101 on its target, was noted to increase proportionally with dose escalation and lasted from 6-24 hours after administration. To date, disease stabilization lasting four cycles or longer (range 4 to 8 cycles) was noted in 5 of 28 patients.

"We are very pleased with the preliminary data from this Phase I trial for solid tumors, as well as the data indicating that both IV and oral dosing are potential routes of administration for PXD101," stated Timothy M. Shannon, M.D., Executive Vice President Research and Development and Chief Medical Officer at CuraGen. "We are also encouraged by the fact that we see evidence of prolonged activity with this drug, observing histone hyperacetylation, a measure of drug target activity, for up to 24 hours after administration."

Based upon these Phase I results and recently reported preclinical data, a Phase Ib study evaluating PXD101 plus 5-fluorouracil (5-FU) for the treatment of solid tumors, including colorectal cancer, will begin enrolling patients by the third quarter of 2005. Furthermore, additional proof-of-concept studies for other types of solid tumors will be initiated throughout 2005 evaluating PXD101 either alone or in combination with other active anti-cancer treatments.

The companies also reported than an abstract discussing a second Phase I clinical trial of PXD101 for patients with advanced hematologic cancers, such as multiple myeloma, was published in the ASCO 2005 Proceedings. Preliminary results from this Phase I study suggest safety and tolerability similar to those reported for patients with advanced solid tumors. CuraGen and TopoTarget anticipate that additional results from this ongoing trial will be presented at a medical conference during 2005. The findings of this study are being further explored in the ongoing Phase II clinical trial for patients with advanced multiple myeloma, a deadly form of blood cancer. This Phase II clinical trial is expected to be complete by mid-2006. Additional proof-of- concept studies in other hematologic cancers will also be initiated in 2005.

About HDAC inhibitors

A growing body of research highlights the role of histone deacetylases (HDAC) in regulating gene expression, particularly the expression of cancer- related genes. HDAC inhibitors represent a new mechanistic class of anti- cancer therapeutics that target HDAC enzymes, and have been shown to: arrest growth of cancer cells (including drug resistant subtypes); induce apoptosis, or programmed cell death; promote differentiation; inhibit angiogenesis; and sensitize cancer cells to overcome drug resistance phenotype when used in combination with other anti-cancer agents. HDAC inhibitors are believed to play a role in a wide range of solid malignancies such as breast, colon, lung and ovarian cancers, and hematological malignancies, such as lymphomas, leukemias and myeloma.

FDA Permits Phase IIb Kidney Transplant Trial

Fri, 13 May 2005 17:44:38 PST

( from http://www.rxpgnews.com ) Isotechnika Inc. announced today that the Company has received permission from the Food and Drug Administration of the United States to proceed with a Phase IIb kidney transplant trial for its lead immunosuppressive drug, ISA247.

The planned randomized, open-label trial will include approximately 332 de novo (newly transplanted) kidney patients from clinical trial sites across North America. The Company previously received a No Objection Letter from Health Canada on April 28, 2005 to begin the Phase IIb kidney transplant trial.

Patients will be placed into one of four separate dosing groups. The four dosing groups will be comprised of three different targeted blood concentrations of ISA247 compared with the fourth group, a tacrolimus control arm. All patients will receive twice daily oral treatment of drug over a 24-week period. Treatment will commence at the time of transplant surgery.

The primary endpoint of the trial is defined as non-inferiority in biopsy proven acute rejection (BPAR) episodes with patients receiving ISA247 for six months as compared to tacrolimus. Additionally, patient's kidney function and other laboratory parameters such as hypertension, hyperlipidemia and new onset diabetes mellitus will be monitored for the duration of the trial.

"We are extremely pleased to receive permission from the FDA to conduct this Phase IIb trial as it validates the bridging studies performed by the Company last year. As a result of changing the manufacturing to the trans-ISA247, it was necessary to complete a number of bridging studies prior to filing for regulatory approval to commence the Phase IIb trial," stated Dr. Randall Yatscoff, Isotechnika's President & COO. "Our goal, subject to available financial resources, is to commence North American site selection and patient recruitment by the end of the current year."

TNFerade(TM) to be Studied for Locally Advanced Pancreatic Cancer Using Electronic Data Capture Solution

Tue, 10 May 2005 20:39:38 PST

( from http://www.rxpgnews.com ) Phase Forward (NASDAQ: PFWD), a leading provider of data management solutions for clinical trials and drug safety, today announced that GenVec, Inc. (NASDAQ: GNVC) has selected Phase Forward's InForm(TM) electronic data capture (EDC) solution to manage a randomized, controlled Phase II clinical trial of its investigational oncology drug, TNFerade(TM).

The trial will assess the clinical benefit of using TNFerade in combination with standard care treatment in patients with locally advanced pancreatic cancer.

GenVec will leverage the InForm solution via Phase Forward's ASP hosting service to obtain direct, real-time access to clinical data and improve the efficiency and quality of clinical trial data collection and management.

GenVec is a biopharmaceutical company focused on the development and commercialization of novel therapies that improve patient care in the areas of cancer and cardiac disease, and to prevent vision loss. Each of GenVec's investigational drugs utilizes the same approach - localized production of a therapeutic protein at the site of disease.

TNFerade causes the production of Tumor Necrosis Factor-Alpha (TNF-alpha) directly within the tumor and is intended for use with standard chemotherapy and/or radiation to improve the clinical outcome for patients. Pancreatic cancer, which is very hard to control with current treatments and can be cured only when it is found at an early stage, is currently the lead indication for TNFerade.

Biopharmaceutical companies like GenVec continue to search for innovative ways to approach clinical data management. Prior to selecting Phase Forward's InForm solution to assist in the trial, GenVec relied on traditional paper-based methods for data collection and management. "It is important that we carefully evaluate technology vendors to ensure that we select a partner that understands our business requirements and is flexible enough to meet our specific needs," said Jennifer Drescher, clinical operations manager at GenVec. "We selected Phase Forward because of its market leadership, experience serving both large and small biopharmaceutical companies in various therapeutic areas, and superior product functionality. The GenVec/Phase Forward team put forth a tremendous effort to not only meet tight deadlines for EDC implementation, but achieve them ahead of schedule."

During the five week treatment period, patients randomized to receive TNFerade will receive chemotherapy and radiation plus a weekly intratumoral injection of TNFerade, followed by gemcitabine maintenance; control patients will receive chemotherapy and radiation alone, followed by gemcitabine maintenance. Progression-free survival, shrinkage of the primary tumor, surgical resectability of the primary tumor following treatment, and overall survival will all be assessed.

InForm will allow GenVec to expedite the collection of high quality data, enhance the execution and management of the TNFerade trial, and improve and accelerate clinical decision-making. Utilizing Phase Forward's ASP hosting service enables GenVec to reap the benefits of EDC without the delays or costs associated with a full on-site technology implementation.

"The American Cancer Society estimates that over 32,000 people will be diagnosed with pancreatic cancer this year, and unfortunately, nearly all of them will die of their disease. Although pancreatic cancer is the fourth leading cause of cancer deaths in men, and the fifth in women, very little headway has been made in terms of prolonging the expected survival of pancreatic patients during the past decade. Phase Forward is honored to serve as GenVec's technology partner in this effort to test a new approach to treating patients suffering from this devastating disease," said Bob Weiler, president and CEO of Phase Forward.

Motexafin Gadolinium Works by Disrupting Key Metabolic Enzymes

Sun, 01 May 2005 20:57:38 PST

( from http://www.rxpgnews.com ) The chemotherapy drug motexafin gadolinium (brand name: Xcytrin, manufactured by Pharmacyclics, Inc.) works to thwart cancer cells by disrupting key enzymes involved in cellular metabolism, according to a team of researchers led by Joseph Hacia, Ph.D., assistant professor of biochemistry and molecular biology at the Keck School of Medicine of the University of Southern California.

The cellular disruption results in increases in the amount of zinc available inside the cancer cells, and because zinc is involved in protein structure and function, leads to inhibition of enzyme activity and to the death of the cells.

A paper describing these findings was published in the May 1, 2005, issue of the journal Cancer Research.

In order to gain a better understanding of the mechanism of action of this novel chemotherapeutic agent, the researchers looked at gene expression profiles and other biochemical properties of cells from human lung, prostate and lymphoma cancer cell cultures that had been treated with motexafin gadolinium, or MGd. What they found was that the drug created oxidative stress in the tumor cells, increasing the levels of expression of the genes that produce metallothioneins.

The researchers showed that the increased metallothionein expression levels resulted from significantly increased levels of free-i.e., not protein-bound-zinc in the cells. The zinc, in turn, acted to inhibit an enzyme-thioredoxin reductase-that is an important component in the cell's antioxidant system, as well as important in DNA synthesis. In other words, thioredoxin reductase is key to the replication and survival of cells, and its inhibition ultimately leads to cell death.

"Our studies showed that MGd induces oxidative stress in cancer cells," says Hacia, who is a member of USC's Institute for Genetic Medicine, "and this leads to disruption of zinc metabolism and alteration of key enzymes and metabolites necessary for normal cell function."

Thus, the researchers noted, the use of MGd leads to the death of cancer cells via disruption of critical enzymes needed for cell survival and replication.

"We have increased the understanding of this drug's mechanism of action," Hacia said of the study, adding that it also may "provide support for the hypothesis that agents that disrupt metabolism and increase intracellular zinc levels have potential applications as anticancer therapeutics."