How Understanding Stem Cell Biology Can Improve Cancer Therapy
Radiation therapy and chemotherapy have traditionally been considered the main forms of cancer treatment. While these treatments can be highly effective, they have significant negative side effects due to their unintended collateral toxicity on normal cells in the body. New treatments are needed to more safely treat cancers, which affect millions of people worldwide every year.
In recent years, the world of cancer therapy has rapidly expanded beyond these broad systemic approaches to include immunotherapy (using the body’s own immune system to kill cancer cells), targeted therapy (using drugs that target specific genetic mutations), and other forms of precision medicine. However, each of these therapeutic advances comes with their own issues of toxicity and, in some cases, they can stop working if people develop resistance to them. To continue to develop new and innovative therapies for cancers, research into tumor biology is needed. One area of research that holds the potential to provide insight into tumorigenesis is stem cell biology.
The relationship between stem cells, development, and cancer has fascinated scientists for over one hundred years. Stem cells generate or regenerate tissues and organs by multiplying and differentiating into more specialized cell types through highly regulated cell division. This cell division is tightly controlled by specific genes both as people develop in the womb and throughout their lives. However, if the genes regulating cell division become mutated, cells can divide out of control, leading to cancer. Understanding the processes of normal cellular development can help identify effective new targets for cancer therapy.
One major unanswered question in the cancer biology field is regarding how a cancer starts, or what is the cell of origin? Scientists wondered, given that stem cells are mainly responsible for dividing and replenishing many adult tissues, can cancer arise from stem cells?
Supporting this hypothesis, scientists have found that skin and intestinal stem cells are more susceptible to becoming tumors than other cells in those organs. Damage to the network of cells that interact with the stem cells in their “niche” can also lead to tumor formation. More research is needed to figure out how these changes lead to cancer so that treatments can be developed to specifically stop these cells from dividing out of control.
Understanding stem cell biology can inform cancer treatment even if stem cells aren’t the cell of origin. Non-stem cells can hijack the mechanisms used by stem cells to rapidly divide, forming a tumor. These tumor cells use genes that are normally involved in development and stem cell division to initiate aberrant growth.
This phenomenon of cancer cells inappropriately turning on developmental genes to initiate a tumor has been observed in almost every type of cancer and has been modeled in several organisms. Recently, researchers in Leonard Zon’s laboratory at Boston Children’s Hospital were able to observe this in a living organism, in this case, the well studied zebrafish. For the first time, researchers could watch a single cell become a tumor in a live animal. Scientists discovered that the first event they could observe on the path to melanoma formation, a type of skin cancer, was the re-activation of genes that are otherwise specific to early embryo development. This unique look into the earliest stages of cancer formation allows researchers to screen for new drugs that prevent cancer from forming.
Although the link between stem cells and cancer is strong, more research is needed to determine the cell of origin of different cancer types. If the cell of origin of cancer can be better understood, more specific diagnostic tools and therapies can be developed. Additionally, understanding the genes that control cell division in development and stem cells will hopefully provide new targets to diagnose, treat, and prevent cancer in the future.
Blog by guest contributor Alicia McConnell, PhD, postdoctoral fellow in the lab of Leonard Zon at Boston Children’s Hospital, MA, USA.