Profiling the molecules that make up a tumor is now a standard of care for many cancer types. The existence of recurrent and targetable genetic alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly-targeted therapies, demands flexible and comprehensive approaches to profile clinically significant genes across the full spectrum of cancers.

In this talk, David Solit will review the Memorial Sloan Kettering Cancer Center (MSKCC) experience from a large-scale, prospective clinical sequencing initiative utilizing a comprehensive assay called MSK-IMPACT. Through this platform, Solit and colleagues have compiled matched tumor and normal sequence data from a unique cohort of more than 15,000 patients with advanced cancer. Using these data, Solit and his team have identified clinically relevant alterations and mutational signatures that were shared among common and rare tumor types. Patients were enrolled on matched clinical trials at a rate of around 11 percent. Pathogenic germline mutations, some of which are predictive biomarkers of drug response, were also identified in a significantly higher proportion of patients than expected. Such a high identification rate suggests that using matched germline sequencing to identify mutant alleles associated with increased heritable risk should be considered in all patients with advanced cancer. To enable discovery of novel biomarkers and deeper investigation into rare alterations and tumor types, all results will be made publicly accessible through the AACR GENIE initiative.

Solit is a medical oncologist, laboratory scientist and the Geoffrey Beene Chair for Cancer Research at the Memorial Sloan Kettering Cancer Center. As a member of the Genitourinary Oncology Service, he specializes in the treatment of prostate and bladder cancers. He is involved in clinical trials, particularly trials of targeted drugs known as kinase inhibitors. As the director of the Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Solit leads a multidisciplinary team of clinicians, geneticists, bioinformaticians and laboratory scientists whose mission is to integrate molecular and clinical information to develop therapies that are individualized to each patient’s cancer.