One of the primary goals of cancer biologists is to better understand how tumors form and how cancer progresses. It’s difficult work because the complex nature of tumors poses a substantial challenge to unlocking cancer’s secrets.
Recent evidence supports the hypothesis that cancer stem cells will continue to support the formation of additional cells that perpetuate tumor growth if not specifically targeted by cancer treatments. This will lead to relapse and cause the cancer to accelerate and spread to other areas of the body.
Thinking about a tumor from a stem cell perspective can help scientists understand why different types of tumors – even within the same cancer type – react differently to various treatments, and why tumor response doesn’t often correlate with survival. A patient’s tumor may shrink, but that result may not translate to increased survival.
Understanding the biology of these cancer stem cells will guide us in developing therapies specifically targeted to destroy them.
The concept of cancer stem cells was proposed many decades ago, but only in the last 20 years have technologies advanced enough to prove the theory correct.
Today, we can isolate individual cells and determine how these different tumor cells behave. For decades, it was assumed that all tumor cells had the same capability to support tumor growth and recurrence. In the late 1990s, novel technologies facilitated the ability to isolate individual tumors cells and to implant these cells into mice without an immune system, thereby allowing human tumors to grow and be studied in the context of a living system.
These experiments demonstrated that all cells were not equally able to initiate and perpetuate tumors. Some were bystanders, while others made up a very small population of cells that were able to fully reproduce tumors. Thus the historic model did not accurately explain cancer biology.
Genetic mutations that give advantages to cancer cells, such as those that help the cell survive or replicate better, underpin both the historic and cancer stem cell paradigms for cancer. Mutations, however, aren’t the only source of cellular diversity in solid tumors. Advantageous mutations need to accumulate in the stem cell population to impact tumor formation and/or behavior over an extended period of time.
Why are you excited about cancer stem cells? What does the future look like?
Patients need new approaches to treating cancer. My excitement around the cancer stem cell paradigm centers on its ability to explain tumor differences and the failure of conventional chemotherapy to meaningfully impact patient survival.
I see a future of cancer treatment free of conventional chemotherapy. Instead, I see targeted medicines that actively find and kill cancer stem cells, in combination with either immuno-oncology drugs to promote better recognition of these cancer stem cells by the immune system, and/or others that complement these medicines to target the uniqueness of cancer stem cells.