About

Lewis A. Chodosh, M.D., Ph.D., is the Perelman Professor in Cancer Biology and serves as the Chair of the Department of Cancer Biology at the University of Pennsylvania Perelman School of Medicine. He is also an Investigator at the Leonard and Madlyn Abramson Family Cancer Research Institute and the Abramson Cancer Center, as well as the Associate Director of Basic Science at the same center. His research focuses on mechanisms of cancer development and progression, with particular interest in breast cancer, tumor dormancy, recurrence, and cancer genetics. Dr. Chodosh employs genetically engineered mouse models, patient samples, and computational biology to study pathways regulating cancer development, metastasis, and resistance to therapy. His work aims to elucidate fundamental principles of tumor biology and translate these findings into clinical applications, including targeted therapies and non-invasive imaging approaches.

Research topics

• Biology
• Cancer research
• Medicine
• Internal medicine
• Cell biology

Selected publications

• Figure 1 from Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence

  2025-02-04

  preprintOpen accessSenior author

  <p><b>A,</b> PGRMC1 is overexpressed in human breast cancers of the basal subtype using PAM50. TMEM97 has the highest expression in luminal B tumors. <b>B,</b> PGRMC1 is overexpressed in hormone receptor–negative cancers. LDLR expression is highest in ER−/HER2+. TMEM97 has the highest expression in ER+/HER2+ tumors. <b>C,</b> PGRMC1 is overexpressed in smaller higher-grade tumors. LDLR and TMEM97 expression is highest in higher-grade tumors.</p>

  PublisherDOI

• Supplemental Table S5 from Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence

  2025-05-13

  preprintOpen accessSenior author

  <p>This shows the association of our proliferation score with established scores like Oncotype Dx and PAM50.</p>

  PublisherOA PDFDOI

• Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial

  Nature Medicine · 2025-09-02 · 22 citations

  articleSenior author
  PublisherDOI

• Supplemental Figure S2 from Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence

  2025-02-04

  preprintOpen accessSenior author

  <p>This shows the association of TK1 with early breast cancer relapse segregated by molecular subtype.</p>

  PublisherDOI

• Supplemental Figure S1 from Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence

  2025-05-13

  preprintOpen accessSenior author

  <p>This shows PGRMC1 expression is increased in ER-, PR-, and triple negative human breast cancers.</p>

  PublisherOA PDFDOI

• Supplementary Figure S3 from Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence

  2025-02-04

  preprintOpen accessSenior author

  <p>This shows that TK1 is associated with early breast cancer relapse.</p>

  PublisherDOI

• Supplemental Table S6 from Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence

  2025-05-13

  preprintOpen accessSenior author

  <p>This shows the trimeric complex correlation with PAM50 ROR.</p>

  PublisherOA PDFDOI

• Residual Breast Cancer Cells Co-opt SOX5-driven Endochondral Ossification to Maintain Dormancy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-10

  preprintOpen accessSenior authorCorresponding

  Abstract Recurrent breast cancer accounts for most disease-associated mortality and can develop decades after primary tumor therapy. Recurrences arise from residual tumor cells (RTCs) that can evade therapy in a dormant state, however the mechanisms are poorly understood. CRISPR-Cas9 screening identified the transcription factors SOX5/6 as functional regulators of tumor recurrence. Loss of SOX5 accelerated recurrence and promoted escape from dormancy. Remarkably, SOX5 drove dormant RTCs to adopt a cartilage-dependent bone development program, termed endochondral ossification, that was confirmed by [ 18 F]NaF-PET imaging and reversed in recurrent tumors escaping dormancy. In patients, osteochondrogenic gene expression in primary breast cancers or residual disease post-neoadjuvant therapy predicted improved recurrence-free survival. These findings suggest that SOX5-dependent mesodermal transdifferentiation constitutes an adaptive mechanism that prevents recurrence by reinforcing tumor cell dormancy.

  PublisherOA PDFDOI

• Supplemental Figure S2 from Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence

  2025-05-13

  preprintOpen accessSenior author

  <p>This shows the association of TK1 with early breast cancer relapse segregated by molecular subtype.</p>

  PublisherOA PDFDOI

• Supplemental Table S4 from Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence

  2025-02-04

  preprintOpen accessSenior author

  <p>This shows the upstream regulators with significant number of targets correlated with PGRMC1</p>

  PublisherDOI

Recent grants

• In Vivo Oncogene-Induced Tumorigenesis and Escape

  NIH · $6.2M · 2003–2029

• NIH Grant R01CA092190

  NIH · $1.5M · 2006

• NIH Grant R01CA083849

  NIH · $1.3M · 2005

• Radiogenomic Biomarkers of Breast Cancer Recurrence

  NIH · $3.1M · 2018–2024

• NIH Grant U54CA155850

  NIH · $10.7M · 2018

Frequent coauthors

• Tien-Chi Pan

  Translational Therapeutics (United States)

  102 shared

• Dhruv K. Pant

  Translational Therapeutics (United States)

  91 shared

• George K. Belka

  Translational Therapeutics (United States)

  87 shared

• Edward J. Gunther

  Penn State Milton S. Hershey Medical Center

  57 shared

• Christopher J. Sterner

  University of Pennsylvania

  47 shared

• Phillip A. Sharp

  Massachusetts Institute of Technology

  44 shared

• Stephen R. Master

  Children's Hospital of Philadelphia

  42 shared

• James V. Alvarez

  Fred Hutch Cancer Center

  42 shared

Labs

• Chodosh LaboratoryPI

Education

• M.D., Medicine

  Harvard Medical School

  1989

• Ph.D., Biology

  Massachusetts Institute of Technology

  1989

• B.S., Biochemistry

  Yale University

  1981

Awards & honors

• Perelman Professor in Cancer Biology
• Associate Director, Basic Science, The Abramson Cancer Cente…
• Chair, Department of Cancer Biology, University of Pennsylva…
• Co-Director, 2-PREVENT Translational Center of Excellence in…