Three researchers who are recipients of a collaborative grant from the Samuel Waxman Cancer Research Foundation have developed a new type of drug designed to kill non-Hodgkin lymphoma tumor cells. The breakthrough could lead to potential non-toxic therapies for cancer patients. The Foundation-funded investigators include Ari Melnick, M.D., of Weill Cornell Medical College, Alexander MacKerell, Ph.D., of the University of Maryland and Gilbert Privé, Ph.D., of the University of Toronto. The researchers, who published their findings in the April issue of Cancer Cell, have identified a drug that targets an oncogene known as BCL6.

BCL6 functions as a master regulatory protein. “It’s a protein that controls the production of thousands of other genes,” said Dr. Melnick, an associate professor of medicine at Weill Cornell Medical College in New York City. “Because of that, it has a very profound impact on cells and is required for lymphoma cells to survive and multiply.”

BCL6 causes the majority of diffuse large B cell lymphomas, the most common form of non-Hodgkin lymphoma. Currently, about 60 percent of diffuse large B cell lymphomas can be cured with chemo-immunotherapy, said Dr. Melnick. “The hope is that we can improve that to a higher percent, and in the long term reduce the need for chemotherapy,” he added.

Traditional cancer drugs target enzymes, which have small pockets on their surfaces that can be blocked with molecules. Until now, pharmaceutical companies have been reluctant to create drugs that target a protein like BCL6 because they function through a different mechanism involving interactions with cofactor proteins involving extensive protein surfaces. “And because the real estate covered by these interactions is so large, the drug companies have viewed these as being not druggable targets,” said Melnick.

He and his colleagues were able to identify a “hot spot” on BLC6 that they predicted would play a critical role in protein interactions. They showed that their BCL6 inhibitor drug was specific to BCL6, and did not block other master regulatory proteins. The drug had powerful lymphoma killing activity and yet was non-toxic to normal tissues. “This is the first time a drug of this nature has been designed and it shows that it’s not actually impossible to target factors like BCL6,” he said.

Emerging data from other investigators suggests that BCL6 is important in many other tumor types, including forms of leukemia.

“The Samuel Waxman Cancer Research Foundation has always supported the collaborative work of scientists, funding innovative cancer research grants,” said Samuel Waxman, M.D., the scientific director of the Foundation. “The Foundation has supported the work of Alexander MacKerell, Ari Melnick and Gilbert Privé for a number of years because we believe their work highlights the critical and important mission of our organization—that collaboration can lead to potential effective cures.”

The Samuel Waxman Cancer Research Foundation Announces Fifth David T. Workman Memorial Award Recipient

Molecular biologist Alan Ashworth, Ph.D., FRS, the director of the Breakthrough Breast Cancer Research Centre at the Institute of Cancer Research in London, will receive the David T. Workman Memorial Award on May 17. The two-year grant of $50,000 from the Samuel Waxman Cancer Research Foundation will be awarded to Dr. Ashworth for his work with PARP inhibitors in BRCA-mutated cancers.

“I’m both surprised and delighted that the Waxman Foundation has thought to honor me in this way,” said Dr. Ashworth. “Recognition from your peers is incredibly important and I’m thrilled.”

Dr. Ashworth helped discover the BRCA2 breast cancer gene in 1995. After realizing that BRCA-related cancers had a flawed DNA repair pathway, Dr. Ashworth and his team worked with a biotechnology company to study the use of PARP inhibitors to treat these cancers. They learned that BRCA-defective cancer cells were 1,000 times more sensitive to PARP inhibitors than cells that were normal. His lab is studying the use of PARP inhibitors to treat cancers such as endometrial cancer, ovarian cancer and breast cancer, including triple-negative breast cancer, which responds poorly to normal chemotherapy.

Speaking about Dr. Ashworth’s research in triple-negative breast cancer, Samuel Waxman, M.D., the Scientific Director of the Waxman Foundation said it represents a contribution from a scientist unraveling a genomic defect in breast cancer that has resulted in a novel treatment for women who would otherwise have a poor prognosis.

Michael Nierenberg, the Chair of the Foundation, added, “The Waxman Foundation is committed to bridging the gap between lab science and the patient. We are excited to help further the important work of Dr. Ashworth and his lab.”

Recent recipients of the Workman award include Stephen Baylin, M.D., and Peter Jones, Ph.D., in 2008 for the development of demethylating agents and epigenetic therapy for hematologic malignancies and Douglas Lowy, M.D., and John Schiller, Ph.D., in 2006 for their advance in preventing cervical cancer with the HPV vaccine.

The Samuel Waxman Cancer Research Foundation, an international organization dedicated to finding effective cures and preventing cancer, has named Gwen Darien as Executive Director. Darien, a 17-year cancer survivor, was editor-in-chief of CR—a magazine serving the cancer survivorship community—and director of the Survivor and Patient Advocacy Program at the American Association for Cancer Research, where she worked to promote partnerships among the cancer survivor, patient advocacy and scientific communities.

“Gwen brings a wealth of expertise and unique skill set to the Foundation,” stated Michael Nierenberg, the Chairman of the Samuel Waxman Cancer Research Foundation’s Board of Directors. “Gwen’s background as a patient advocate, knowledge of cancer research and relationships with members of the scientific community will help further our mission to cure and prevent cancer.”

“More than ever before, scientists are developing promising strategies to reprogram cancer cells. For decades, the Samuel Waxman Cancer Research Foundation has been a leader in finding cures with minimal toxicity for patients,” said Samuel Waxman, M.D., the Foundation’s Scientific Director. “I am thrilled that Gwen is part of the Foundation. I know that under her leadership, the Foundation will continue its important work of supporting innovative cancer research.”

Darien is chair of the NCI Director’s Consumer Liaison Group and is a member of the Health and Human Services’ Secretary’s Advisory Committee on Genetics, Health and Society. She serves on the program committee of the Accelerating Anti-Cancer Agent Development and Validation Workshop. Darien also serves on the advisory board of the Health Advocacy Program at Sarah Lawrence College and is an external adviser to the Breast Cancer SPORE at the Duke Comprehensive Cancer Center.

“I am honored to serve as the Executive Director of the Samuel Waxman Cancer Research Foundation and am deeply committed to research that will bring real benefit to patients,” said Darien. “I look forward to working with the Foundation’s Board and stakeholders to develop partnerships, strategic alliances and collaborations across all segments of the cancer community to help fulfill the Foundation’s incredible potential and sustain its critical mission.”