The Stem Cell

Scott Dylla is a senior scientist at Oncomed Pharmaceuticals, a small biotechnology company focused on developing novel therapeutics targeting cancer stem cells. He trained at Stanford University with Irving Weissman.

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by Scott Dylla, Ph.D.

Seven years into the 21st Century, cancer continues to be the #1 cause of death worldwide. Although therapeutic response rates and time to progression have dramatically improved, long-term survival has not changed for most, if not all, solid tumors such as those of the lung, breast, and colon. Past decades of cancer research and drug development have largely considered all tumor cells equal in status and potential for harm. This is no longer the case, as rare subpopulations of tumor cells are being identified as responsible for fueling tumor growth. These cancer stem cells (CSC) appear more resistant to chemotherapy and radiation than most cells within the tumor, explaining why tumor regression following such therapies is so common. Furthermore, because newer therapies composed of antibodies or small molecules have been developed against bulk tumor cells and not the CSC population, it is unlikely that cures for cancer will be imminent until the scope of attention is focused on the CSC population itself.

Normal stem cells serve to support tissue growth and maintenance over the lifetime of an individual. Cancer stem cells, on the other hand, appear to be black sheep of the stem cell family and best resemble a normal tissue-specific stem cell gone awry. Although normal cells are generated, the growth rate and cell organization are highly abnormal because the CSC parents are generating too many offspring; ultimately resulting in masses of dysfunctional tissue. Because CSC have been differentiated from the majority of cells within a tumor that can be likened to branches of a tree, novel therapies with better efficacy will likely be aimed at the roots of the tumor (i.e. CSC). Realistically, the next generation of cancer therapies will target molecules on the cell surface, or within the cell, that CSC utilize to proliferate or survive as long-lived stem cells. Ideally, these therapeutic targets will not be expressed on normal stem cells such that there will be little damage to normal tissue.

Yet, the identification, isolation, and experimental manipulation of CSC from solid tumors poses major obstacles. As might be imagined, ripping cells away from their neighbors, upon which they are largely dependent, is no easy task. Developing assays that further allow CSC manipulation to learn about their biology is even more difficult. I’m often asked when there will be a “cure for cancer.” My answer is often that the term cancer encompasses many diseases and the war will be won in a progression of smaller battles. I am encouraged by my daily work with CSC that commonalities can be exploited to vastly improve not only treatment, but detection of cancer at earlier stages where therapies may be most beneficial.