In less than a decade, multigene testing on next-generation sequencing platforms has fundamentally altered the understanding, definition and treatment of cancer. By making it possible to locate and characterize somatic alterations in cancer cells, whole-exome sequencing has furthered molecular analysis of the disease and helped identify new therapeutic targets.
The process is still in the early stages, however. Finding which variants, among hundreds, drive disease and which are irrelevant has proved challenging. And it is unlikely that a single variant or epigenetic effect is common to all cancers or even all cancer cells within the same patient. Even so, the way forward seems certain. Cancer will no longer be identified primarily by the tissue of origin but rather by its genomic profile, and targeted cancer drugs will be matched to a tumor's genetic changes.
Earlier this year, Mayo Clinic moved fully into translational genomics by opening its Individualized Medicine (IM) Clinic on all three Mayo campuses. Unlike Mayo's research-oriented Center for Individualized Medicine, the IM Clinic focuses exclusively on integrating advances in genomic science and gene sequencing into clinical practice.
Konstantinos N. Lazaridis, M.D., enterprise director of the clinic, explains it is not an experiment or clinical trial, but rather "a consulting service within Mayo that is using genomics technologies such as whole-exome sequencing to find solutions for patients with serious conditions."
The clinic currently offers consulting for diagnostic odyssey cases and for people with advanced solid tumor cancers who have failed standard therapy. Within these parameters, patients are screened and accepted on a case-by-case basis.
Because it can take months to receive whole-exome sequencing test results, most patients start with a smaller panel test that is returned in two or three weeks. Even so, genomic sequencing is not for people for whom time is of the essence. For cancer patients who qualify, the process involves identifying genomic alterations in cancer-related genes and searching for therapeutic agents that more effectively target them.
Gianrico Farrugia, M.D., who directs the Center for Individualized Medicine in Minnesota, notes, "This is not whimsical sequencing, but a comprehensive and professional approach aimed at serious problems. This is what we've been working toward since the genome was mapped."
The IM Clinic is an integrated center, with representatives drawn from across Mayo, including 20 physicians trained in genomics as well as genetic counselors, bioinformaticians, pathologists, bioethicists and medical champions — physicians with backgrounds in genetics who follow individual cases to ensure primacy of the clinical perspective. A genomic tumor board composed of experts from all three sites meets weekly to review, analyze and interpret each patient's genomic data.
"The IM Clinic and the genomic tumor board provide a forum for multidisciplinary experts from the clinical, genetic and ethical sides to personalize a care plan for the patient," explains oncologist Robert R. McWilliams, M.D., advanced cancer IM Clinic director in Minnesota. "This information is communicated to the primary, tumor-specific oncologist within our group to then finalize the treatment plan in the context of the patient's overall clinical situation. The IM physicians can subsequently aid with identification of appropriate trials or obtaining access to agents through other means, such as single-patient IND or expanded access programs."
Close to 35 patients have been seen at the IM Clinic, many with analyses still ongoing. About half have received recommendations for therapy based on genomic findings. Although numbers are small at this point, some patients appear to have benefited from the recommended targeted therapies.