Dr. Sznol on Unanswered Questions With Immunotherapy in RCC

Mario Sznol, MD
Published: Friday, Mar 22, 2019



Mario Sznol, MD, professor of medicine, co-director, Yale SPORE in Skin Cancer, Yale Cancer Center, discusses unanswered questions with immunotherapy in the treatment of patients with renal cell carcinoma (RCC).

There are many unanswered questions in this space, Sznol says, including the need for effective biomarkers. Immunotherapy has had a significant benefit in select patients, but researchers don’t quite understand the biology that is driving response or resistance. RCC is a disease with a low to moderate number of mutations, so it is still a bit of a mystery as to why the cancer can be responsive to immunotherapy. Potential answers to this question, Sznol notes, include the expression of endogenous retroviruses or more indels. However, the fact that RCC is almost as responsive to immunotherapy as a highly mutated disease, such as melanoma, is somewhat puzzling.

While response rates to immunotherapy in patients with RCC are promising, there aren’t many durable responses. The question then becomes, “If a patient is not responding to these therapies, what are the reasons for this?” Sznol says there could be 20 to 30 different reasons, which means there are 20 to 30 possible combination strategies to overcome this. However, one combination for all patients is not going to work.
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Mario Sznol, MD, professor of medicine, co-director, Yale SPORE in Skin Cancer, Yale Cancer Center, discusses unanswered questions with immunotherapy in the treatment of patients with renal cell carcinoma (RCC).

There are many unanswered questions in this space, Sznol says, including the need for effective biomarkers. Immunotherapy has had a significant benefit in select patients, but researchers don’t quite understand the biology that is driving response or resistance. RCC is a disease with a low to moderate number of mutations, so it is still a bit of a mystery as to why the cancer can be responsive to immunotherapy. Potential answers to this question, Sznol notes, include the expression of endogenous retroviruses or more indels. However, the fact that RCC is almost as responsive to immunotherapy as a highly mutated disease, such as melanoma, is somewhat puzzling.

While response rates to immunotherapy in patients with RCC are promising, there aren’t many durable responses. The question then becomes, “If a patient is not responding to these therapies, what are the reasons for this?” Sznol says there could be 20 to 30 different reasons, which means there are 20 to 30 possible combination strategies to overcome this. However, one combination for all patients is not going to work.



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