Immunotherapy has been making headlines as one of the most significant breakthroughs in cancer care in decades. The anti-cancer drugs Keytruda and Opdivo have led the way as immuno-oncology treatments that have brought a second chance at life to patients who had no other hope. However, not all patients respond to the treatments. Now, researchers believe they know why, and how it could help point them to a different treatment option.
According to a Feb. 6 press release from UCLA, researchers led by Dr. Antoni Ribas, director of the UCLA Jonsson Comprehensive Cancer Center Tumor Immunology Program, found that the popular immunotherapy drug Keytruda, a PD-L1 inhibitor, may not work effectively in patients harboring the JAK1 and JAK2 genetic mutations. The researchers found that when the tumors in melanoma and colon cancer patients lost a gene called B2M, JAK1 and JAK2 were found to “function improperly” and prevented the immune system from successfully fighting back the cancer cells.
The higher presence of JAK1 and JAK2 led to a loss of PD-L1 expression that is critically important for pembrolizumab to effectively attack the cancers. Other research has shown the presence of JAK1 and JAK2 in some mesothelioma tumors.
“These mutations result in a genetic mechanism for the absence of reactive PD-L1 expression, and patients harboring such tumors would be unlikely to respond to PD-1 blockade therapy,” said the researchers.
Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells. Keytruda has been met with success among some mesothelioma patients, including Mavis Nye of England who is now an eight year survivor of the cancer and is the first patient from the UK to claim remission of the disease.
Like many cancers, mesothelioma is an aggressive cancer that is challenging to treat. This research is critical for ensuring mesothelioma patients are considered for the appropriate treatment. Personalized care targeted to a patient’s unique mesothelioma characteristics optimizes the potential for success of the treatment and offers treatment options that may not otherwise have been considered.
The researchers are currently studying animal models with JAK1 and JAK2 genetic mutations to “help develop new and improved combination treatments for people who do not respond to anti-PD-1 treatment.”
For more information see the study in the Feb. 5 issue of Cancer Discovery.