HOUSTON - Researchers at The University of Texas MD Anderson Cancer Center will test combinations of targeted therapy and immunotherapy against lung cancer driven by an untreatable genetic mutation and seek to prevent ovarian cancer in women at high risk for the disease, vital objectives of two new Stand Up to Cancer Dream Teams.
The teams, announced Monday at the annual meeting of the American Association for Cancer Research, are the latest national collaborative efforts funded by Stand Up to Cancer, an organization started in 2008 by film and media leaders to accelerate the translation of cancer research into advances in patient care.
The projects selected for the Dream Teams mark national expansion of research under way in MD Anderson's Moon Shots Program, also designed to speed the conversion of scientific discoveries into clinical advances that reduce cancer deaths.
"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 Ron DePinho, M.D.
"Both the need and challenges are great, but so are the opportunities. 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,." DePinho said.
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 the center's role in ovarian cancer.
Lung cancer: Thwarting KRAS mutations
The Stand Up to Cancer (SU2C)-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."
Heymach and colleagues have been studying KRAS and ways to attack it as part of the GEMINI flagship of the Lung Cancer Moon Shot. (See: New subsets of lung cancer with KRAS gene mutations identified)
Their role in the SU2C project will focus on combining targeted therapies with immune checkpoint blockade against KRAS-mutant lung cancer. The project will include preclinical research and clinical trials. "We have strong leads indicating that this type of combination is the most promising approach," Heymach said.
The targeted therapy will be MEK inhibitors, which research indicates might be active against KRAS, combined with immune checkpoint blockade drugs that block activation of an off switch molecule called PD1 on immune system T cells.
Heymach is principal investigator of this aspect of the Dream Team. MD Anderson researchers also will operate the project's database and biostatistics core, oversee organization and analysis of images collected in clinical trials, and conduct immune profiling on all clinical samples. Other team members include:
- Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and scientific director of the Moon Shots immunotherapy platform.
- Patrick Hwu, M.D., head of the Division of Cancer Medicine and chair of Melanoma Medical Oncology.
- Jack Lee, Ph.D., associate vice provost for Quantitative Research.
- David Piwnica-Worms, Ph.D., M.D., chair of Cancer Systems Imaging.
- Vali Papadimitrakopoulou, M.D., professor, and Kathryn Gold, M.D., assistant professor, both of Thoracic/Head and Neck Medical Oncology, will lead combination clinical trials.
Ovarian cancer: Saving lives through prevention
The Stand Up To Cancer (SU2C)-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 to better treat and prevent ovarian cancer.
High-grade serous ovarian cancer is the most common and lethal form, comprising 70 percent of all cases, 90 percent of which are at advanced stages when diagnosed. Efforts continue to develop screening tests to identify the disease at earlier, more treatable stages, but so far none exists. About 20 percent 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 Shot, 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 analysis of all MD Anderson patients with either cancer. Those with BRCA1 or 2 mutations are offered treatment with new drugs that treat defects caused by those aberrations.
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. "It's called cascade testing - we start with the patient and when mutation is confirmed, cascade to the family, and that includes sisters, daughters, nieces, aunts, cousins," Lu said.
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 telephone. Those proceeding to test are sent saliva collection kits.
These procedures are designed to overcome barriers to testing, which include the need to travel to cancer centers for counseling and testing. The Dream Team project will use a nine-gene panel to analyze risk.
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. These issues are often barriers to preventive surgery for women who now may choose only standard of care.
MD Anderson launched the first pilot study of fallopian tube removal surgery last year and expects to report early outcomes next year.
The lung cancer Dream Team will be led by Jeffrey Engelman, M.D., Ph.D., associate professor of medicine at Harvard Medical School, with Jedd Wolchok, M.D., Ph.D., chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center in New York, as co-leader.
Alan D'Andrea, M.D., co-director of the Gene Therapy Center at Dana-Farber Cancer Institute in Boston, will lead the ovarian cancer Dream Team. Elizabeth Swisher, M.D., professor in the Department of Obstetrics and Gynecology at the University of Washington in Seattle, will be co-leader.
About MD Anderson
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 41 comprehensive cancer centers designated by the National Cancer Institute (NCI). For the past 25 years, MD Anderson has ranked as one of the nation's top two cancer centers in U.S. News & World Report's annual "Best Hospitals" survey. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672).