SUMMARY
Peter C. Lucas, M.D., Ph.D., is a pathologist and physician-scientist who investigates the role of dysregulated inflammatory signaling pathways in cancer. Dr. Lucas and his team are leveraging their discoveries in signal transduction to develop novel therapeutic approaches to restore antitumor immunity for a variety of cancers. As such, Dr. Lucas' work lies at the interface of oncology and immunity.
Dr. Lucas is co-principal investigator of the Oncoimmune Signaling and Therapeutics Laboratory as a joint initiative with his wife, Linda M. McAllister, M.D., Ph.D. Their laboratory has been continuously supported by R01 funding from the National Institutes of Health (NIH) since 2008.
Drs. Lucas and McAllister study how dysregulated inflammatory signaling mediators, such as NF-kB, JNK, JAK/STAT and STING, impact both the behavior of cancer cells and the cells of the tumor immune microenvironment. A key objective is to understand how dysregulation of these oncoimmune signaling pathways in cancer cells can allow these cells to communicate with both innate and adaptive immune cells to establish a tumor immune microenvironment that favors growth and subsequent metastatic dissemination.
Focus areas
- The CBM signalosome in non-Hodgkin lymphoma. Early in their careers, Drs. Lucas and McAllister made a series of critical discoveries that led to a new understanding of the molecular mechanisms responsible for driving non-Hodgkin lymphoma. Specifically, they characterized a novel signaling complex composed of the proteins CARMA1, BCL10 and MALT1 (the CBM signalosome) and showed that while this complex is critical for normal immunity, genomic alterations that affect its activity play a central role in the pathogenesis of several subtypes of non-Hodgkin lymphomas and leukemias. Their work now focuses on approaches to specifically target CBM activity by developing novel small-molecule therapeutics to disrupt assembly of the signalosome.
- The CBM signalosome in breast cancer. The Lucas-McAllister team is studying the connection between the CBM signalosome and triple-negative breast cancer. Their team is studying how hyperactivation of the CBM signalosome drives upregulation of the immune checkpoint protein PD-L1 and promotes secretion of multiple immunosuppressive factors that together impair the activity of neighboring immune cells.
- HER2-positive breast cancer. Drs. Lucas and McAllister discovered that a truncated form of the HER2 oncoprotein, called p95HER2, which is expressed in a subset of HER2-positive breast cancers, drives tumor immune suppression and resistance to HER2-targeted therapies. Their team is now developing a clinically viable assay for p95HER2 expression. In addition, the team is working with medical oncology colleagues to launch a clinical trial to specifically target p95HER2 and restore antitumor immunity in HER2-positive cancers where upregulation of p95HER2 is identified.
- Brain and liver cancers. Other research projects center on the role of dysregulated MALT1 signaling in glioblastoma and hepatocellular carcinoma.
Significance to patient care
Dr. Lucas hopes his research with Dr. McAllister leads to new treatments for cancer. By studying how cancer cells send signals to other cells, they intend to find better ways to stop cancer and help the body's immune system fight back. Their goal is to use what they learn to make cancer treatments more effective so patients have a better chance of recovery.
Professional highlights
- Mayo Clinic:
- Chair, Division of Experimental Pathology and Laboratory Medicine, 2025-present.
- Vice chair for research, Department of Laboratory Medicine and Pathology, 2024-present.
- Breast Cancer Research:
- Deputy editor, 2022-2023.
- Associate editor, 2020-2022.
- UPMC Hillman Cancer Center:
- Director of translational pathology, 2019-2023.
- Hillman Fellow for Innovative Developmental Cancer Research, 2019.
- Director of pathology, NSABP Foundation-NRG Oncology, 2016-2023.
- Elected member, The American Society for Clinical Investigation (ASCI), 2014.