Personalized medicine is new watchword

The National Comprehensive Cancer Network (NCCN) recently sponsored a roundtable discussion called Cancer Care in the 21st Century-Reality and Promise. The panelists discussed a wide range of topics, including the most important advances in cancer care since the war on cancer was declared during the Nixon Administration in 1972 and how pharmacogenomics is revolutionizing cancer treatment. The roundtable meeting, at which the group of oncology leaders assembled for the first time, took place during the NCCN 11th Annual Conference, held recently in Hollywood, Fla.

"In the past 10 years, dozens of cell-signaling pathways have become better defined," Donald L. Trump, M.D., chair of the department of medicine and senior VP for clinical research at the Roswell Park Cancer Institute in Buffalo, N.Y., told Drug Topics in a later interview. "These pathways control mitosis, cell maturation and differentiation, cell adhesion and motility, and apoptosis."

In another separate interview, Saïd Sebti, Ph.D., program director of the H. Lee Moffitt Cancer Center & Research Institute's Drug Discovery Program, told Drug Topics, "The way we will treat cancer in the future can best be described as 'personalized medicine.' The therapy will be tailored to the characteristics of the tumor found in each individual."

Sebti said that the drugs that look the most promising inhibit angiogenesis and mitosis, prevent metastases, or promote apoptosis. He mentioned that a company called Sugen, which was acquired by Pfizer when it bought Pharmacia in 2003, is developing several compounds that block vascular endothelial growth factor (VEGF).

Sebti explained that although VEGF is important for the initiation of angiogenesis, malignant cells also need platelet-derived growth factor (PDGF) to maintain new blood vessels. He and his colleague Andrew Hamilton, Ph.D., of Yale University, have developed a novel molecule, GFB-204, that binds both VEGF and PDGF and blocks the binding of these growth factors to their receptors. According to Sebti, his team is about one year away from receiving Food & Drug Administration approval to take GFB-204 into clinical trials.

"Hopefully, this molecule will be more effective than bevacizumab [Avastin, Genentech] against breast tumors, which rely heavily on PDGF to grow and metastasize," Sebti said. "Bevacizumab only blocks VEGF, which is why it is so effective against VEGF-dependent colorectal tumors, but it is ineffective against breast tumors."

Promoting the apoptosis of malignant cells is another strategy for cancer treatment. In cancerous cells, the serine-threonine kinase Akt becomes abnormally hyperactivated and is responsible for tumor survival, no matter what drugs you try, Sebti said. "Akt is a very hot molecular target right now, because we know that in animal models, if you block Akt, tumor cells die," he said. "Here at Moffitt, in collaboration with Jin Q. Cheng, M.D., Ph.D., a professor at the University of South Florida in Tampa, we were able to identify one Akt inhibitor, triciribine phosphate [TCN-P, or VQD-002, VioQuest Pharmaceuticals]." They plan to start enrolling patients for a clinical trial very soon.