A tumor’s genome provides an incredibly large amount of information — but it’s not always enough to point oncologists toward an effective drug. Dr. Christopher Kemp and colleagues at Fred Hutchinson Cancer Research Center take cancer genomics several steps further, integrating genomic information with high-throughput screening methods that pinpoint known drug susceptibilities and potential drug targets. The strategy is already bearing fruit in a trial of a new drug against head and neck cancer. Now, Kemp and his collaborators have secured two new National Cancer Institute grants, totaling more than $7 million, to take their approach further.
“We can’t drug many of the most commonly mutated genes found in in cancer,” Kemp said. “There are spectacular examples of success in treating cancer based on DNA-sequence information, but these are seen in a small minority of patients. And even when these therapies work, the tumors often recur and develop drug resistance.”
Sometimes, drugs that target a specific mutation don’t work as well as expected in a patient; sometimes no drugs exist that can target a tumor’s specific array of mutations. These challenges require a new approach.
Kemp’s approach, termed functional genomics, focuses directly on patients’ tumor cells. It melds the descriptive information found in a tumor’s genomic profile with functional information gleaned from high-throughput screening of tumor cells for susceptibilities to certain drugs and potential vulnerabilities found in cancerous, but not healthy, cells. The approach can be applied toward different types of cancer and clinical problems such as identifying new drug targets, tackling drug resistance or pinpointing which drugs will work best for an individual patient’s tumor.
Now, the two new grants will help Kemp and colleagues identify new drug targets in difficult-to-treat cancers and bring the approach to other researchers and oncologists. Currently, the team is focusing on head and neck, breast, pancreatic and ovarian cancers.
A $4.3 million, five-year grant from the NCI’s Cancer Target Discovery and Development Network (CTD2) is an extension of a grant Kemp received in 2013 and will support the use of functional genomics to identify new drug targets in KRAS/TP53-mutant pancreatic cancer and drug-resistant ovarian cancer. During the grant’s initial four years, Kemp teamed up with Fred Hutch’s Drs. V.K. Gadi, Carla Grandori (now at SEngine Precision Medicine), and the late Eduardo Méndez to study breast and head and neck cancers. They identified WEE1 as a unique vulnerability in p53-mutated head and neck tumors, which led to a clinical trial testing a WEE1-targeting drug in patients with these tumors.
The second award, also from the NCI, provides $3.1 million over five years to help Kemp and colleagues translate their approach to the public via a commercial entity. With partners at Oregon Health Sciences University and SEngine Precision Medicine, a company that Kemp and Hutch colleagues established to fulfill the promise of personalized oncology, the team plans to develop this functional genomics approach into a CLIA-approved assay that can both accelerate academic drug discovery and help oncologists deliver individually tailored therapies to cancer patients.
Both projects are made possible by teamwork and collaboration between experts in different fields, including cancer biologists, clinicians, and computational scientists, Kemp said.
“There’s no way this is going to happen in one person’s lab,” he noted.
Collaborators on the two projects span several Pacific Northwest research institutions and include Hutch colleague and SEngine co-founder Dr. V.K. Gadi, Hutch colleague Dr. Jerry Radich, SEngine CEO Dr. Carla Grandori, Drs. Barbara Goff and Elizabeth Swisher at the University of Washington School of Medicine, Dr. Ilya Shmulevich at the Institute for Systems Biology, and Dr. Brian Druker, director of the Knight Cancer Institute at OHSU.