Breakthroughs in cancer research that have the biggest clinical impact often start from novel findings within a single cell.
Recent work published in Nature Cell Biology by Philip Howe, PhD, of Cancer Biology, Lerner Research Institute, in collaboration with colleagues from the laboratory of Paul Fox, PhD, of Cell Biology, Lerner Research Institute, reveals a novel mechanism that may help target destruction of late-stage cancer cells while leaving non-cancerous cells alone. This scenario could play-forward to a time when the devastating effects of chemotherapy are a thing of the past.
Here's the idea. Since cancer involves cell growth, it is understandable that cancer high-jacks pathways responsible for normal growth. One such pathway involves a molecule called "TGF-β," short for "transforming growth factor-beta." This "TGF-β" promotes late-stage cancer growth, which is marked by metastatic spread of the tumor.
One thing that normal growth patterns (as seen during embryonic development) and metastatic cancer have in common is a process known as "EMT," or "epithelial-to-mesenchymal transition," which is driven by TGF-β.
So cancer can cause TGF-β to induce EMT, and this enables cells to move, allowing the cancer to spread, which is a key component of metastasis. But how? If that can be identified, scientists could be well on the way to stopping it.
Dr. Howe and colleagues present substantial insight in their recent article. They have identified that TGF-β induces EMT by regulating two genes in a novel manner. Furthermore, they identified specific pathway components, which, if inhibited, could prevent the activation of these genes and therefore presumably block cancer progression.
Importantly, since EMT is normally silenced in adulthood (but active in adult cancer), inhibiting active EMT could potentially affect only the cancerous adult tumor cells. Currently one of the major drawbacks of chemotherapy is that the very nature of the drugs poisons all cells – both the good and the bad. The devastating effect on the "good" cells results in chemotherapeutic side-effects, which today's cancer-prevalent society knows all too well. Being able to reduce the effect on non-cancerous cells would mean greatly reduced side-effects and a tremendous advance in the treatment of adult cancers.
This plausible mechanism of countering metastatic tumor spread has never before been realized, and could be a key component in identifying prognostic markers or developing targeted chemotherapy.