Siddhartha Mukherjee uses his experience as a trainee in Boston to talk about cancer stem cells in Sunday’s NYTimes Magazine. The story is adapted from his upcoming book, Emperor of All Maladies: A Biography of Cancer. Here, he talks about a patient who relapsed, like many others, after responding to the much-touted “targeted therapy” Gleevac.
But what if my patient’s cancer had never actually died, despite its invisibility on all scans and tests? CT scans, after all, lack the resolution to detect a single remnant cell. Blood tests for cancer also have a resolution limit: they detect cancer only when millions of tumor cells are present in the body. What if her cancer had persisted in a dormant state during her remissions — effectively frozen but ready to germinate? Could her case history be viewed through an inverted lens: not as a series of remissions punctuated by the occasional relapse, but rather a prolonged relapse, relieved by an occasional remission?
In fact, this view of cancer — as tenaciously persistent and able to regenerate after apparently disappearing — has come to occupy the very center of cancer biology. Intriguingly, for some cancers, this regenerative power appears to be driven by a specific cell type lurking within the cancer that is capable of dormancy, growth and infinite regeneration — a cancer “stem cell.”
If such a phoenixlike cell truly exists within cancer, the implication for cancer therapy will be enormous: this cell might be the ultimate determinant of relapse. For decades, scientists have wondered if the efforts to treat certain cancers have stalled because we haven’t yet found the right kind of drug. But the notion that cancers contain stem cells might radically redirect our efforts to develop anticancer drugs. Is it possible that the quest to treat cancer has also stalled because we haven’t even found the right kind of cell?
Boston doctors working on cancer stem cell research include Kornelia Polyak at Dana Farber: She summed up the state of the art in the 2009 abstract from the journal Current Opinion in Genetics & Development
Cancer stem cells and their potential roles in tumor heterogeneity are currently subjects of intense investigation. Studies suggest that these cells may develop from any normal cell and have begun to elucidate their molecular profiles. The percentage of a tumor composed of cancer stem cells varies greatly, and researchers believe that multiple types of these cells may exist in a single neoplasm. Cancer stem cells may be formed by epithelial-mesenchymal transition and seem to be less prevalent in metastases than in corresponding primary tumors. These cells appear to have therapeutic sensitivities different from those of cancer cells with more differentiated features. Looking into the many questions that remain about the cancer stem cells model might lead to more effective cancer prevention, diagnosis, and treatment.
From a hospital press release: June 1, 2007
Researchers from Children’s Hospital Boston and the Dana-Farber Cancer Institute have identified the cancer stem cell for rhabdomyosarcoma, the most common soft-tissue sarcoma of childhood. They report their findings in the June 1 issue of Genes & Development. Cancer stem cells make up only a small fraction of the overall number of cells in a tumor, but are capable of giving rise to other cancer cells, and thereby drive tumor growth and metastasis. The rhabdomyosarcoma stem cell is one of a handful of cancer stem cells identified to date, and the first to be identified by studying zebrafish.
The zebrafish recapitulates human rhabdomyosarcoma very closely,” says Leonard Zon, MD, Director of the Stem Cell Program at Children’s Hospital Boston, Grousbeck Professor of Hematology/Oncology at Children’s and the study’s senior investigator. “Using zebrafish as a model, we identified a type of cell, called the cancer stem cell, that is capable of remaking the tumor. It is these cells that are retained after chemotherapy and cause patients to relapse. If one can target these rare cells for destruction, the hope is that tumors will not re-grow.”