Normal cells in a tumor may aid and abet melanoma and other cancers
A recent discovery indicates that healthy cells within a tumor may supply factors that help cancer cells sharing the tumor microenvironment grow despite the presence of anticancer drugs.
Cancer cells grown in test tubes died in the presence of many targeted cancer agents, but when normal cells were included in the mix, the cancerous cells developed resistance to more than half of the 23 agents tested. In the specific case of melanoma, drugs targeting a common mutation in the BRAF gene showed great success against tumors in some patients, but not in others.
“We can take cancer cells out of a melanoma patient, put them on a dish, and most times they will turn out to be extremely sensitive to targeted agents, but that's not what we see in patients,” commented Ravid Straussman, first author of the study and a postdoctoral fellow at the Eli and Edythe L. Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, Massachusetts. His group's findings were published in the journal Nature (2012;487:500-504).
As part of their investigation into the mechanisms behind this phenomenon, Straussman and colleagues measured more than 500 factors secreted by normal cells in melanomas. They found that the factor most closely linked to BRAF-inhibitor drug resistance was hepatocyte growth factor (HGF). HGF interacts with the MET receptor, and although abnormal activation of the MET receptor has been tied to tumor growth, it had never been associated with drug resistance in melanoma. Tumor samples from 34 persons with melanoma demonstrated that the tumors in the patients with low HGF levels shrank more than those in the patients with high HGF levels.
According to a statement from the Broad Institute, several HGF/MET inhibitors are in clinical development or are FDA-approved for other indications, making clinical trials that combine these agents with BRAF inhibitors feasible.