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Michael DiGiovanna, MD, PhD

Professor of Internal Medicine (Medical Oncology); Chair, Breast Cancer Tumor Board, Yale Cancer Center; Curriculum Director, Office of Education; Thread Leader, Pharmacology, Office of Education; Master Course Co-Leader, Office of Education

Contact Information

Michael DiGiovanna, MD, PhD

Research Summary

We study signal transduction by growth factor receptor tyrosine kinases, focusing on the EGFR/HER2/ErbB family, including the impact of signaling by these receptors on clinical outcomes and response to targeted therapies for cancer, and their potential as therapeutic targets in novel combination therapies. A major focus in our laboratory has been the interaction of HER2 signaling with estrogen receptor (ER) signaling in breast cancer, and with IGF-I receptor signaling, and the effects of inhibitors of these receptors in combination targeted therapies. We have also found that in breast cancer patients, tumors harboring activated HER2 have adverse prognosis, and these tumors have co-overexpression of EGFR. We continue to study how signaling by these receptors impacts responses to different types of therapies and explore targeting these receptors in combination with other novel targeted therapeutics.

Specialized Terms: Breast cancer; HER-2/neu/ErbB-2; IGF1 receptor; EGF receptor; Growth factor receptor tyrosine protein kinases in malignancy; Estrogen receptor; Signal transduction; Breast cancer clinical trials

Extensive Research Description

We study signal transduction by growth factor receptor tyrosine
kinases, focusing on the EGFR/HER2/ErbB family, including the impact of
signaling by these receptors on clinical outcomes and response to
targeted therapies for cancer, and their potential as therapeutic
targets in novel combination therapies. A major focus in our laboratory
has been the interaction of HER2 signaling with estrogen receptor (ER)
signaling in breast cancer, and with IGF-I receptor
signaling, and the effects of inhibitors of these receptors in
combination targeted therapies. We have also found that in breast
cancer patients, tumors harboring activated HER2 have adverse
prognosis, and these tumors have co-overexpression of EGFR. We continue
to study how signaling by these receptors impacts responses to
different types of therapies and explore targeting these receptors in
combination with other novel targeted therapeutics.

Coauthors

Research Interests

Breast Neoplasms; Medical Oncology; Pharmacology; Protein-Tyrosine Kinases; Signal Transduction; Clinical Trial

Selected Publications

Clinical Trials

ConditionsStudy Title
BreastAn Open-Label Phase II Trial to Evaluate the Efficacy and Safety of Neoadjuvant Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel Plus Trastuzumab and Pertuzumab in Early Stage HER2-Negative Breast Cancer Patients Selected With a Test Measuring Live Cell HER2 Signaling Transduction (FACT 1)
BreastThe CompassHER2 Trials (Comprehensive Use of Pathologic Response Assessment to Optimize Therapy in HER2-Positive Breast Cancer) CompassHER2 Residual Disease (RD), a Double-Blinded, Phase III Randomized Trial of T-DM1 Compared With T-DM1 and Tucatinib
BreastA Randomized Phase II Trial Of Circulating Tumor DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer
BreastRandomized Non-Inferiority Trial Comparing Overall Survival of Patients Monitored With Serum Tumor Marker Directed Disease Monitoring (STMDDM) Versus Usual Care in Patients With Metastatic Hormone Receptor Positive Breast Cancer
Breast - FemaleI-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
BreastA Phase 3, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) Versus Investigator's Choice of Chemotherapy in Patients Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy in First-line Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION Breast02)
BreastA Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endocrine Therapy Plus Everolimus in Patients With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer