Patricia S. Steeg, a National Cancer Institute Chief and the Wife of Riderwood's Medical Director, Calls for New Direction in Oncology

May 31, 2012

SILVER SPRING/BETHESDA, MD (May 31, 2012) -- Patricia S. Steeg , the wife of Dr. Gene Machado, Riderwood retirement community's  Medical Director, and daughter of Riderwood resident Elizabeth Wiegand,  has published an article in Nature magazine that calls for a new direction in oncology, particularly with respect to clinical trials for treating breast cancer.  Steeg is Chief of the Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
"The oncology community as a whole needs to commit to doing something different," Steeg writes.
She writes: "Cancer therapeutics inhibit tumor growth, but there is more to cancer than growth. To reduce the incidence of metastatic disease, drug development should target the metastatic process itself. Metas­tases are distinct from the primary tumor, in terms of both the tumor cells themselves, which have different mutations and gene-expression profiles, and the surrounding microenvironment. As such, they pro­vide opportunities for developing new lead compounds.
"Metastasis-preventive compounds could block any number of steps in the metastatic process: invasion (or escape) of cells from the primary tumor into the bloodstream, survival in the circulation, avoidance of the immune system, arrest and egress from the circulation (when, for example, circulating tumor cells get stuck in a capillary and escape into the tissue through the blood-vessel wall), or successful colonization of a distant organ," Steeg writes.
"There is a huge barrier to developing agents that prevent breast can­cer metastasis. If such agents were tested in the current clinical-trial system, many would fail. Simply put, clinical trials are not designed to test metastasis-preventive compounds," she writes.
A new clinical-trial design is needed, according to Steeg. "This design must incorporate pre­clinical and clinical data in a rational manner and measure end points that are appropriate for metastasis prevention. I propose a detour from the linear model of clinical development either before or just after phase II trials.
"I recommend that randomized phase II trials be carried out for metastasis prevention," she writes.  "These trials would test compounds that have been shown to prevent metastasis in animal studies, that have few side effects in phase I trials and that work safely with existing drug combinations in the clinic. The trials would enroll selected patients --- those who are at high risk of recurrence or who already have limited metastatic disease --- who would be rand­omized to receive either the candidate preventive agent or a placebo. The most important end point would be the time until a new metastasis occurs --- not shrinkage of an existing tumor."