Approaches to cancer treatment developed by MD Anderson researchers as part of the institution’s Moon Shots Program will be, in part, the focus of two new Dream Teams announced by Stand Up to Cancer (SU2C), a national organization launched by film and media leaders to speed development of cancer treatments.
The researchers will test combinations of targeted therapy and immunotherapy against lung cancer driven by intractable KRAS mutations and will seek to prevent ovarian cancer in women at high risk for the disease.
The teams, announced this week at the annual meeting of the American Association for Cancer Research, are the latest national collaborative efforts funded by SU2C, which assembles Dream Teams of prominent researchers to address specific issues.
“We’re honored MD Anderson experts have been invited to collaborate with the exceptional team assembled by Stand Up to Cancer, and we look forward to nationally expanding our ongoing research efforts focused on these deadly cancers,” said MD Anderson President Ronald DePinho, M.D. “Through these collaborations and vital support from SU2C, we have the potential to make a profound impact for the benefit of patients throughout the world.”
John Heymach, M.D., Ph.D., chair of Thoracic/Head and Neck Medical Oncology, leads MD Anderson’s lung cancer team, and Karen Lu, M.D., chair of Gynecologic Oncology and Reproductive Medicine, heads MD Anderson’s role in ovarian cancer.
The Stand Up to Cancer-American Cancer Society Lung Cancer Translational Research Dream Team is a $20 million, multi-institution effort to rein in cancers driven by mutations in the KRAS gene.
“The biggest unmet challenge in lung cancer is finding a way to target KRAS mutations,” Heymach said. “They are the most common types of mutations — between 22 to 30 percent of patients with non-small cell lung cancer have KRAS mutations — and right now, there are no drugs for these patients.”
The American Cancer Society reports that approximately 85% of lung cancers are non-small cell lung cancers.
Heymach and colleagues have been studying KRAS and ways to attack it as part of the GEMINI flagship of the Lung Cancer Moon Shot. (For a deeper dive, read: "New subsets of lung cancer with KRAS gene mutations identified")
Heymach’s team will focus on combining targeted therapies called MEK inhibitors with immune checkpoint blockade against KRAS-mutant lung cancer.
Ovarian cancer: Saving lives through prevention
The Stand Up To Cancer-Ovarian Cancer Research Fund (OCRF)-Ovarian Cancer National Alliance (OCNA)-National Ovarian Cancer Coalition (NOCC) Translational Research Dream Team is a $6 million project involving five institutions.
High-grade serous ovarian cancer is the most common and lethal form, accounting for 70% of all cases, 90% of which are at advanced stages when diagnosed. About 20% of all cases are caused by inherited genetic mutations that greatly heighten a woman’s risk for developing the disease.
“So many women in this high-risk group are unidentified, we think successfully identifying them and offering them preventive surgical options provides a significant opportunity to reduce mortality from this disease,” said Lu, co-leader of the Dream Team’s prevention project.
The Dream Team will launch such an effort based on a project started in 2012 as part of the Breast and Ovarian Cancer Moon Shots, which focuses on high-grade serous ovarian cancer and triple-negative breast cancer, which share molecular similarities. BRCA1 and BRCA2 gene mutations increase risk of developing either cancer.
The moon shot offers universal genetic testing of all MD Anderson patients with either cancer. Those with mutations are offered treatment with PARP inhibitors, which address defects caused by the mutations.
Working with patients who test positive for the mutations, MD Anderson researchers conduct outreach to family members to educate them about genetics and offer them testing to assess risk. The Dream Team project is “an extension of that. It’s about improving accessibility to genetic testing and empowering family members to test,” Lu said.
Called the CHECMATE trial (Chance to End hereditary ovarian Cancer by Making Testing Better and Easier), the study will use innovative web-based education programs and genetic counseling over the phone. Those proceeding to test are sent saliva collection kits.
A second aspect of the Dream Team is testing new preventive measures. The project will compare standard of care, which is removing the fallopian tubes and ovaries, to a novel option of first removing only the fallopian tubes with the ovaries to be removed later.
Lu said research indicates that high-grade serous ovarian cancer starts in the fallopian tubes. Delaying removal of the ovaries avoids early menopause and preserves quality of life. MD Anderson launched the first pilot study of fallopian tube removal surgery last year and expects to report early outcomes next year.