FDA Center for Drug Evaluation and Research (CDER), agreed, adding, “Companies can no longer successfully develop groundbreaking therapy in isolation. The era of doing this solo is over.”

Perhaps the most important reason for collaboration is to speed up the process of drug development so that effective treatments are delivered sooner to cancer patients, who may not have time on their sides. “Patients have a real sense of urgency. We can’t wait,” noted Dr. Jane Perlmutter, patient advocate and founder of the Gemini Group.

“We have been developing targeted agents for one pathway or target at a time, and that hasn’t necessarily yielded the type of breakthrough therapies for patients that we are looking for,” said Dr. Stuart Lutzker, vice president of Oncology Exploratory Clinical Development at Genentech. “From a sponsor’s perspective, there has been an extremely high failure rate.”

Several speakers elaborated on that theme by pointing out different reasons why most patients do not respond or eventually become resistant to targeted therapies. Many of these treatments target a single biochemical pathway to inhibit the activity of a kinase enzyme that fuels tumor growth, but as Dr. Jeffrey Engelman, assistant professor of medicine at Harvard Medical School and director of Thoracic Oncology at Massachusetts General Hospital, noted, “Most cancers are not really that sensitive to a perturbation of a single kinase pathway.” He described how certain breast and gastric cancers are “addicted” to receptor tyrosine kinases,1 such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2/neu), and a kinase called MET.2 In some cases, when these receptors are blocked with targeted therapies, tumor cells die and patients go into remission. Two major downstream signaling pathways emanate from these receptor tyrosine kinases—the PI3K (phosphatidylinositol 3-kinase)-AKT3 pathway and the MAPK (mitogenactivated protein kinase) pathway. These pathways foster tumor growth by promoting cell division and inhibiting cell death. Consequently, when

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1 Kinases are a type of enzyme that can activate molecules in a cell, and some cancer treatments target certain kinases that are linked to cancer. Receptor tyrosine kinases are a type of cell-surface receptor important in normal cellular processes and the development and progression of certain types of cancer.

2 EGFR binds to epidermal growth factor, causing cell division. In some cancers, EGFR is found at abnormally high levels on cells. The HER2/neu protein is a tyrosine kinase receptor involved in normal cell growth and is abnormally active in some types of cancer. MET is a tyrosine kinase receptor protein involved in wound repair that is abnormally activated in some cancers.

3 AKT is a kinase that is involved in cell growth and proliferation, survival, and motility. It has been implicated as a major factor in many types of cancer.



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