The SU2C-American Cancer Society Lung Cancer Dream Team Progress Update
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The SU2C-American Cancer Society Lung Cancer Dream Team Progress Report
Targeting KRAS Mutant Lung Cancers
Leader: Jeffrey A. Engelman, MD, PhD; Massachusetts General Hospital
Co-Leader: Jedd Wolchok, MD, PhD; Memorial Sloan Kettering Cancer Center
Fast Facts on Lung Cancer
- Lung cancer is the second most common cancer in both men and women and by far the leading cause of cancer death in the United States.
- In the United States, an estimated 158,040 deaths occurred from lung cancer in 2015.
- The best way to reduce lung cancer risk is not to smoke. Breathing in other people’s smoke can also increase your risk of developing lung cancer.
Lung cancer is the leading cause of cancer death in the United States. Mutations in a gene called the KRAS gene are found in 20 to 25 percent of lung cancers. Cancers that are driven by KRAS mutants do not respond well to standard lung cancer treatments and are notoriously difficult to treat. Fortunately, targeted therapies that specifically inhibit the protein that is produced by the mutant KRAS gene are being developed bring promise to patients. In addition, a new class of drugs, called immune checkpoint inhibitors, is showing promising results in a number of cancers including lung cancer. Checkpoint inhibitors work by releasing a brake placed by the tumor on the patient’s own anti-cancer immune system.
The goal of the SU2C-American Cancer Society Lung Cancer Dream Team is to develop and bring together these two highly promising therapeutic approaches of targeted therapy and immunotherapy. Researchers from top Cancer Centers across the country have come together to collaborate towards this goal of new and successful treatments that they hope will markedly improve outcomes for patients with KRAS-mutant lung cancer.
The Team is taking a three-pronged approach to create new treatments for KRAS-mutant lung cancer. First, the most effective therapies for targeting the mutant KRAS protein and related biological pathways will be identified. Second, approaches to exploit the immune system for the treatment of KRAS-mutant lung cancers will be developed. Third, targeted therapies with immunotherapies will be integrated as a novel combination treatment approach to treatment of KRAS-mutant lung cancer.
The Team of collaborators is an unrivaled group of experts from both fields of targeted therapies and immunotherapy. Bringing the remarkable advances in these two fields together will quickly lead to new therapies for patients with KRAS mutant lung cancers.
In the first 6 months, the Dream Team has made significant progress in all of the planned areas of investigation.
- Work has been initiated in the study of new drugs that block the mutant KRAS protein.
- They have also begun to assemble an unprecedented collection of tumor and blood specimens from patients treated with PD-1 inhibitors, a type of checkpoint blocker immunotherapy, learning more about why some patient’s tumors respond to these drugs, while others do not.
- Critical studies in state-of-the-art laboratory animal model systems to explore the best way to combine KRAS blocking medicines with immunotherapies were initiated.
In the next 6 months, the Team will continue enrollment in clinical trials, collection and analyses in patient specimens, and optimization of preclinical models and immunotherapy dosing strategies.
In the 7-12 month period, the Dream Team continues to make to significant progress in all planned research goals.
- The Team has implemented a comprehensive infrastructure to analyze tumor samples from lung cancer patients treated with the immunotherapy agent called PD-1 inhibitor.
- They have revealed a mechanism of action for KRAS inhibitors, which allows for the development of more rational drug combinations using this class of drugs.
- They have identified new inhibitors that work in combination with KRAS inhibitors and are testing these combinations in pre-clinical models, including one specific drug combination, which includes trametinib (FDA-approved for melanoma).
- Clinical trial enrollment is progressing with three of ten open clinical trials.