Precision medicine at UNC: Looking for cancer-driving gene mutations across cancers

UNC Lineberger will be enrolling patients into a new, national clinical trial, known as NCI-MATCH, that will group patients based on the genetics of their tumors as opposed to where their cancer is located. The new initiative will test more than 20 drugs or drug combinations targeting specific genetic mutations.

Precision medicine at UNC: Looking for cancer-driving gene mutations across cancers click to enlarge Juneko Grilley-Olson, MD

UNC Lineberger Comprehensive Cancer Center researchers are leading an emerging scientific approach to cancer treatment that is building on advances in genetic sequencing. In this investigational approach to cancer treatment, patients are treated based on the genetic mutations found in their cancer.

Cancer center oncologists have been designing and enrolling patients in clinical trials known as “basket trials" to test this approach. In these basket trials, patients are selected for treatment for targeted drugs based on whether they have certain mutations or molecular alterations. The strategy represents a shift away from treating patients based on where their tumors originated, as patients are eligible for a trial if their tumors are found to have a specific mutation– regardless of where their cancer was first diagnosed in the body.

“Historically, we looked to treat cancers based on where they started in the patient,” said Juneko Grilley-Olson, MD, a UNC Lineberger member and medical oncologist. “But now, we understand that sometimes molecular changes found across different types of cancers leads to a more sophisticated way to treat them.”

This approach will be tested in a new, nationwide clinical trial co-developed by the National Cancer Institute. For this trial, known as the Molecular Analysis for Therapeutic Choice Trial, or NCI MATCH trial, several thousand people are expected to be screened for molecular alterations. About 1,000 patients are expected to be enrolled, and more than 20 drugs or drug combinations targeting a specific genetic mutation are expected to be tested, according to the NCI. Enrollment is expected to begin in July for the trial's first 10 arms. Grilley-Olson is co-chair for a future trial am that's planned to study the use of drugs targeting the phosphoinositide 3-kinase (PI3K) enzyme pathway.

“NCIMATCH is a unique, groundbreaking trial,” said Doug Lowy, MD, NCI acting director, in a prepared statement in a release by the NCI. "It is the first study in oncology that incorporates all of the tenets of precision medicine. There are no other cancer clinical trials of this size and scope that truly bring the promise of targeted treatment to patients whose cancers have specific genetic abnormalities. It holds the potential to transform cancer care.”

Already, UNC has led a variety of basket trials outside of NCI-MATCH, Grilley-Olson said, including trials with pharmaceutical companies. There are two separate industry-sponsored trials currently ongoing at UNC, she said, including one trial that will test a handful of drugs shown to target four different mutations, including one for people with mutations in the BRAF gene. Drugs have been approved for people with advanced melanoma with a specific BRAF mutation, but the new trial will test the drug in patients with other types of cancer as well.

“By using treatments targeted to molecular alterations in individual tumors, we are putting precision medicine into practice.” -Juneko Grilley-Olsen, MD, medical oncologist

“Remarkable” advances in genetic sequencing, as well as in the understanding of cancer have made such a treatment approach possible, Grilley-Olson said. Cancer is now understood fundamentally as a genetic disease, with molecular alterations or abnormalities driving the uncontrolled growth of cells. The sequencing of an individual patient’s tumors is becoming standard of care. Patients at the N.C. Cancer Hospital are having their tumors sequenced as standard of care in a state-of-the-art pathology facility, or when further analysis is needed, as part of a clinical trial called UNCseq.

“Those results can be placed in the patient’s medical record, thus enabling any treating physician to know what alterations may be driving the cancer, and thereby being better able to identify patients for trials such as these basket trials,” Grilley-Olson said. The new approach to treatment will hopefully open doors for possible treatments for patients with diseases that have otherwise limited options and allow researchers to identify cancer types that may or may not be responsive to these drugs.