In recognition of the major contribution he is making to the field of basic cancer research, UCSF Comprehensive Cancer Center Director Frank McCormick has received the 2002 Unrestricted Cancer Research Grant from the Bristol-Myers Squibb Foundation. The $500,000 award will allow
McCormick and his colleagues to carry out a new approach to elucidating all of the genes of key cell pathways regulating cancers.
McCormick has also been honored with the Forty-second Annual American Association for Cancer Research (AACR) - G.H.A. Clowes Memorial Award.
The Bristol-Myers Squibb five-year, $500,000 research grant is intended to allow premier research institutions to pursue new avenues of research at their discretion. McCormick, referred to as “one of the fathers of molecular cancer biology” in a Bristol-Meyers Squibb Foundation press release, has pioneered research on the altered molecular pathways that fuel the development and growth of cancers.
Signal transduction pathways determine how cells respond to their environment, how they regulate the cell cycle and many other crucial aspects of their behavior. In cancer, the normal controls regulating these pathways are subverted. Understanding the molecular missteps that disrupt these key pathways is already leading to new advances in cancer treatment, as new therapies target proteins in these complex pathways.
“We’re really pleased,” said McCormick. “Our aim is to integrate the growing database of genetic changes that occur in cancer cells, with our knowledge of signaling pathways and cancer biology, so that we can identify new relationships between pathways that could lead to new approaches to cancer therapy. This holistic approach can only be achieved with state-of-the-art informatics that can cope with the tremendous complexity of genetic and biological changes that are typical of cancer cells. From this complexity, we expect to extract new insights that will help guide our efforts towards new therapies and better use of existing ones.”
“Under Dr. McCormick’s leadership, scientists at UCSF are tackling the most complex, unanswered questions in cancer biology,” said Robert Kramer, PhD, vice president, Oncology and Immunology Drug Discovery at Bristol-Myers Squibb Pharmaceutical Research Institute in Princeton, New Jersey. “This covers a wide range of approaches that include the elucidation of cancer susceptibility genes that predispose individuals to increased cancer risk. In addition, they are seeking to understand the interactions between normal tissues and cancer cells that are thought to be critical in cancer progression.”
McCormick’s other honor, receipt of the 2002 American Association for Cancer Research’s G.H.A. Clowes Memorial Award, recognizes his seminal contribution to studies of the structure and function of the genes that cause cancer. As the recipient of this award, he will give an award lecture at the 93rd AACR Annual Meeting in San Francisco, April 7, 2002.
McCormick is the second UCSF researcher in three years to receive the AACR G.H.A.Clowes Award. Elizabeth Blackburn, PhD, UCSF professor of biochemistry and biophysics, received the award in 2000 for her research on telomeres, segments of DNA that bind both ends of chromosomes, and telomerase, an enzyme that produces telomeres. Telomerase is a potential target for cancer therapy.
“I’m grateful for the recognition the AACR is giving me, and hope that the work at the UCSF Comprehensive Cancer Center will continue to contribute to advances in cancer research,” says McCormick.
McCormick’s studies have focused on determining the way in which cancer-causing genes, known as oncogenes, function, with the goal of disabling them. His work has focused on the Ras oncogenes and the role they play in cancer, and on new ways of applying knowledge about oncogenes and tumor suppressor genes to the development of cancer therapies. His work on the Ras signaling pathway has led to the discovery of an inhibitor of a key enzyme regulated by Ras, a kinase referred to as Raf. Inhibition of this pathway stops cancer cells from growing, and sensitizes them to killing by radiation or conventional chemotherapy agents. The new Ras inhibitor has recently completed Phase I clinical evaluation, and joins a group of kinase inhibitors that are advancing through clinical testing at many institutions, including the UCSF Comprehensive Cancer Center.
In 1992 McCormick developed a novel therapy, Onyx-015, that uses a crippled form of the common cold virus, the adenovirus, to attack cancerous cells while leaving normal cells healthy. The drug currently is being evaluated in a Phase III clinical trial (the final step before FDA approval) for head and neck cancer at Onyx Pharmaceuticals, where McCormick is a scientific advisor. Scientists at Onyx Pharmaceuticals recently reported that in a Phase II trial of the drug for head and neck cancer, tumors in 63 percent of the patients treated with a combination of Onyx-015 and chemotherapy shrank by 50 percent or more, and in 8 of these 19 responding patients, the tumor disappeared altogether. The approach of using engineered viruses to kill cancer cells has been developed by several biotechnology and pharmaceutical companies, and could become a new platform for cancer treatment in the future.