Yale School of Medicine New Haven, Connecticut
Professor of Medicine Chief, Breast Medical Oncology Co-Director, Yale Cancer Center Genetics and Genomics Program
Identifying novel therapeutic targets in patients with aggressive breast cancer.
While major advances have been made in breast cancer treatment, many patients still face limited options when their cancer stops responding to standard therapies. Antibody-drug conjugates (ADCs), which deliver chemotherapy directly to cancer cells, have shown great promise, but current approved ADCs only target a small number of molecular cancer markers, and not all patients benefit. At the same time, breast cancers are highly diverse, even within a single tumor, and cancer cells can behave differently and respond unevenly to treatment. These challenges highlight the urgent need to discover new drug targets and develop a better understanding of the complex makeup of breast tumors, providing more options to patients and hope for long term benefit.
Dr. Pusztai and his team identified a protein called Nectin-2, which is present in about 70 percent of breast cancers, and are developing novel ADCs that bind Nectin-2 specifically. In laboratory experiments, one of these ADCs was especially effective at destroying breast cancer cells. In parallel, they are studying how different cancer cell types can coexist within the same tumor, finding that tumors with mixed estrogen receptor levels often behave more like aggressive, treatment-resistant subtypes.
Dr. Pusztai and his team are now testing their novel Nectin-2 targeting ADCs in experiments that closely model human breast cancer and in cancers that no longer respond to currently approved ADC treatments. If successful, the new ADC could move into clinical testing, adding to the advanced targeted therapeutic options for aggressive breast cancer.
Lajos Pusztai, MD, DPhil is Professor of Medicine at Yale University and Chief of the Breast Medical Oncology Section at the Yale Cancer Center. He is also Co-Director of the Cancer Center Genomics and Genetics Program. Dr. Pusztai received his medical degree from the Semmelweis University of Medicine in Budapest, and his DPhil. degree from the University of Oxford in England.
His research group has made important contributions to establish that estrogen receptor-positive and-negative breast cancers have fundamentally different molecular, clinical and epidemiological risk characteristics. He has been a pioneer in evaluating gene expression profiling as a diagnostic technology to predict chemotherapy and endocrine therapy sensitivity and have shown that different biological processes are involved in determining the prognosis and treatment response in different breast cancer subtypes. His group has also developed new bioinformatics tools to integrate information from across different data platforms in order to define the molecular pathways that are significantly disturbed in individual cancers and could provide the bases for future individualized treatment strategies. He made important contributions to clarify the clinical value of neoadjuvant chemotherapy in different breast cancer subtypes.
Dr. Pusztai is also principal investigator of several clinical trials investigating new drugs and potential response markers. He has published over 200 manuscripts in high impact medical journals and is the Clinical Editor of the British Journal of Cancer, Member of the Scientific Advisory Board of the Breast Cancer Research Foundation, Member of the Breast Cancer Steering Committee of the NCI and Co-Chair of the Trans-ALTTO Committee that oversees the translational research projects of tissues collected during two larger randomized clinical trials (ALTTO and NeoALTTO). He is also Chair of the Data Safety Monitoring Committee of the OPTIMA trial.
2002
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