A new study sheds light on how molecular subsets within the tumors of kidney cancer patients determine treatment outcomes and underscores the importance of personalized medicine in making therapy decisions.
The study published Thursday, Nov. 5, in Cancer Cell is a comprehensive molecular analysis of 823 tumors donated by patients with advanced renal cell carcinoma (RCC) who were either treated with the immunotherapies atezolizumab and bevacizumab in combination or the targeted therapy sunitinib.
Researchers validated for the first time the prognostic and predictive capability of transcriptional signatures and described the distinct molecular subtypes that associate with different outcomes to these cancer treatments. They also identified additional molecular targets for future drug development.
“These data were a massive undertaking and are the most comprehensive analysis of RCC tumors from a phase 3 trial to date. They further refine the known angiogenic and inflammatory biology of RCC, but also shed light on proliferative and metabolic pathways that are relevant.” said Brian Rini, MD, Ingram Professor of Cancer Research and chief of Clinical Trials at Vanderbilt-Ingram Cancer Center (VICC), the study’s senior author.
Approximately 25% of renal cell carcinoma patients have metastatic cancer at the time of diagnosis, and studies of tumors taken from those patients indicate that 20% of those specimens include a sarcomatoid component. Patients with metastasized cancer whose tumors that include a sarcomatoid component have poor clinical prognosis. Of the 823 tumors studied, 134 had sarcomatoid features.
The researchers identified seven tumor subsets for renal cell carcinoma, including those with sarcomatoid features. The seven molecular subsets are identified in an illustration on the first page of the study along with which treatment had better efficacy. The seven subtypes are Angiogenic/Stromal, Angiogenic, Complement/W-oxidation, T-effector/Proliferative, Stromal/Proliferative and snoRNA.
These data can be used to tailor a biomarker-based approach to select specific therapies for specific patients. This will require further validation of these clusters in prospective trials.
The study highlights the importance of personalized medicine and molecular tumor boards in guiding treatment decisions. Molecular tumor boards are composed of highly specialized cancer experts, including genomics specialists. VICC has a molecular tumor board composed of medical oncologists, molecular pathologists, lab scientists, genetics counselors and bioinformatics experts.
