The Piro Lito Lab
Research
The Lito lab investigates the properties of oncoproteins that drive cancer cell growth, with a focus on cancers driven by RAS mutations. RAS mutants were historically thought to be locked in an active state due to an inability to break down the nucleotide GTP. Contrary to this long-held view, we discovered that mutant RAS transitions between its active and inactive states — and demonstrated how the ability to cycle can be exploited therapeutically by inhibitors targeting either of its states. We identified cellular proteins and pharmacologic approaches that enable mutant RAS to hydrolyze GTP, thus restoring its natural GTPase function and leading to its physiologic inactivation in cancer cells. We co-led the first-in-human trial of an inhibitor targeting KRAS(G12C), the most common RAS mutation in lung cancer, work that culminated in the first FDA-approved therapy for patients with this form of lung cancer. We showed how tumors adapt to RAS inhibition, uncovered genetic mechanisms of resistance in patients, and identified combination therapies that can improve patient outcomes. Together, these findings have advanced our understanding of RAS-driven tumor biology and promise to benefit a broad population of patients, who had limited treatment options in the past. This work has been recognized with the Trailblazer Prize for Clinician Scientists by the Foundation of the National Institutes of Health and the Seldin-Smith Award for Pioneering Research by the American Society for Clinical Investigation.
Research Projects
Featured News
People
Piro Lito, MD, PhD
Enid A. Haupt Chair in Therapeutic Research
- The Lito lab investigates the properties of oncoproteins that drive cancer cell growth, with a focus on cancers driven by RAS mutations.
- MD, PhD, Michigan State University
- View physician profile
- Physician profile
Members
Achievements
- 2022 Life Sciences Breakthroughs of the Year
- ASCI Seldin Smith Award (2022)
- 2022 Pershing Square Sohn Prize for Young Investigators
- FNIH Trailblazer Prize for Clinician Scientists (2021)
- Josie Robertson Investigator (2016-2021)
- Pew-Stewart Scholar for Cancer Research (2019)
- Damon Runyon Clinical Investigator (2017)
- The V Foundation for Cancer Research, Translational Research Award (2015)
- LUNGevity Foundation, Career Development Award (2015)
- NIH K08, Mentored Clinical Scientist Research Career Development Award (2015)
- Stand up to Cancer Lung Cancer Dream Team, Young Investigator (2015)
- Conquer Cancer Foundation, Young Investigator Award (2013)
- Charles A. Dana Fellow/Clinical Scholar in Biomedical Research (2011)
