PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation.

Throughout my career in science, my work has focused in aspects of steroid hormone (progesterone, estrogen, or androgen) receptor activity in breast and prostate cancers. These interests include not only mechanistic studies of receptor activity in treatment naive tumors, but also the role of these receptors in the evolution of resistance to current therapies.

Despite the development of improved therapies, breast cancer remains a leading cause of mortality in women. While a majority of breast cancers are estrogen receptor (ER) positive and respond to endocrine therapies such as tamoxifen or aromatase inhibitors, as many as 50% of patients experience relapse and progression. Recent data has confirmed continued reliance of these cancers on ER signaling, validating this receptor as a therapeutic target even in a relapsed/metastatic setting. The focus of a majority of my work in breast cancer has been the mechanistic evaluation of methods to target ER activity in this setting of resistance, either through the development of improved receptor antagonists or through the identification of targets downstream of, or impinging upon, ER activity that can serve as secondary targets in this setting. 

Similarly, the androgen receptor (AR) remains a therapeutic target in prostate cancer throughout treatment progression to end stage prostate cancer. Although several AR antagonists have been developed and approved for the treatment of prostate cancer, AR overexpression, as well as mutation and/or truncation, are observed clinically and have been shown mechanistically to render the current AR antagonists ineffective in the advanced prostate cancer setting. As with our work in breast cancer, we have identified pathways downstream of AR that are essential to prostate cancer progression, and our current work is intended to devise treatment regimens that will be effective in lieu of, or together with, AR antagonists.

In my role as a research assistant professor, I have conducted several animal studies evaluating next-to-clinic therapeutics in clinically predictive models of advanced breast and prostate cancer that I have developed throughout the past several years of studies. The entry of some of these therapeutics, or of mechanistically related molecules, into clinical trials in these patient populations validates this approach.

Breast cancer angiogenesis
Breast cancer in younger women
Hormonal therapy
Neoadjurant therapy for breast cancer

Current Clinical Investigations

Principal Investigator, A Phase I-II Study of Neoadjuvant Evacet/Paclitaxel/Hyperthermia in Locally Advanced Breast Cancer Patients.

Investigator, Development of Screening Markers for Breast Cancer using Circulating Immune Complexes: Collaborative Study with Diagen Medical Technologies.

Principal Investigator, Use of Plasma D-Dimer as a Predictive Marker in Colorectal Carcinoma: Correlative Science Study with Genentech, Inc.

Principal Investigator, A randomized, Phase II study of gabapentin or glutamine to prevent the peripheral neuropathy/myalgia associated with weekly taxol administration in metastatic breast and lung cancer.

Investigator, A Phase 2, Randomized, Double-Masked, Multicenter Study of Two Dose Levels of ERA-923 for the treatment of Metastatic Breast Cancer in Postmenopausal Women who have failed Tamoxifen therapy. Genetics Institute.

Investigator, A Phase I Study of Combined Doxil/Hyperthermia in Stage IV Breast Cancer.

As Vice Chair for Translational Research in the Department of Pathology, I am involved in numerous translational cancer research projects that rely on the study of human biological samples.  I am the director of the Duke BioRepository & Precision Pathology Center (Duke BRPC), a shared resource of the School of Medicine and the Duke Cancer Institute.  I serve as the PI for the National Cancer Institute's Cooperative Human Tissue Network Southern Division (a five-year UM1 grant), which lives in the Duke BRPC.  My own area of research interest is gastrointestinal tract metaplasias and their relationship to carcinogenesis, particularly in the upper GI tract.

Lab Website

The research in our group is focused on the development and application of mechanism based approaches to identify novel therapeutics for use in the treatment and prevention of hormonally responsive cancers. Specifically we are interested in the pharmaceutical exploitation of the estrogen and androgen receptors as therapeutic targets in breast and prostate cancers and in defining how these receptors influence the pathogenesis of these diseases. These efforts have led to the discovery of several drugs that are currently being evaluated in the clinic as cancer therapeutics, and to the identification of potential biomarkers and predictors of response that can help to target the use of these new drugs. Most recently we have explored approaches to treat triple negative breast cancer and have identified an important pathway that links obesity/dyslipidemia and cancer risk.

Our laboratory uses genomic and pharmacological approaches to understand how tumor dependencies are shaped by cell intrinsic factors, environmental factors, and drug treatments during the dynamic process of tumor evolution. To learn more, please visit our laboratory website: https://woodlabduke.com/.