ASCO Connection recently followed up with Conquer Cancer Foundation grant recipient Shanu Modi, MD, of Memorial Sloan-Kettering Cancer Center (MSKCC). Dr. Modi received the 2009 Advanced Clinical Research Award (ACRA) in Breast Cancer, supported by the Breast Cancer Research Foundation (BCRF).

AC: What were the outcomes of your ACRA in Breast Cancer research, “PU-H71: A Novel HSP90 Inhibitor for the Treatment of Breast Cancer”?

Dr. Modi: I was fortunate to receive the ACRA to support a phase I clinical trial of the novel and promising HSP90 inhibitor PU-H71 for the treatment of patients with advanced cancer. This phase I trial is now well underway, currently enrolling to the third-dose level without evidence of any dose limiting toxicity up to this point. This trial will continue enrollment until we define the maximum tolerated dose or the recommended phase II dose of PU-H71, at which point we will expand the program to tumor-specific phase II studies, including trials for patients with triple-negative breast cancer where the preclinical data for PU-H71 was particularly compelling. Additionally, our phase I trial incorporates novel and exciting correlative studies including serial tumor biopsies and non-invasive PET imaging using the 124I-PUH71 radiotracer as a biomarker of response to therapy. These correlatives should facilitate an expeditious clinical development of this agent allowing the selection of patients most likely to benefit from HSP90 inhibition with PU-H71, and at the same time, set a new paradigm for future targeted drug development.

AC: How has the ACRA in Breast Cancer grant impacted your career?

Dr. Modi: The ACRA has provided me with an incredible opportunity to perform cutting-edge translational research, collaborate with experts in the field at a high level of science and knowledge on a common project, and learn from those experts’ mentorship and example. PU-H71 was developed by one of our own scientists, Dr. Gabriela Chiosis, and the clinical trial incorporates the ideas of many respected colleagues and collaborators at MSKCC.  For me, this project has been a professionally rewarding experience and I hope to put into use the diverse knowledge I’ve acquired as I move forward in future research ventures.

AC: What are you currently working on?

Dr. Modi: I am committed to studying the field of heat shock protein chaperones and their application to the field of oncology. Our early success with the prototype HSP90 inhibitor 17-AAG (tanespimycin) in patients with HER2+ breast cancer has been the foundation for my current research.  PU-H71—a novel purine-based HSP90 inhibitor—has superior preclinical efficacy, pharmacokinetics, and therapeutic index compared to 17-AAG. It has significant antitumor effects in models of triple-negative breast cancer, which has not been seen with other HSP90 inhibitors. Our phase I trial is the first step in evaluating the potential of this new therapy for breast cancer, in particular for triple-negative breast cancer.

In parallel and conjunction with these clinical studies, I am interested in identifying biomarkers of response and resistance to HSP90 inhibition and—in particular, with my collaborators at MSKCC—have an interest in developing non-invasive PET imaging as a means to studying their in vivo pharmacokinetics and pharmacodynamics. In this way, I hope we can expedite the optimal development of these agents either as monotherapy or in combinations, and bring the first HSP90 inhibitor to approval.

AC: Do you have any advice for an early-career oncologist selecting a track or specialty?

Dr. Modi: For me, a career in breast cancer was an obvious choice. The excitement of the advancing research in this field plus the example of my exceptional mentors and colleagues, combined with my affection and connection to this patient population, led me to this path. Finding a supportive mentor who is committed to you and following your interests will always take you to where you should be.

AC: How do you balance research and practice?

Dr. Modi:, I am lucky to be able to do both! I  devote a large part of my time to clinical research, including the PU-H71 project, but I also see and treat patients with breast cancer in the clinic two days a week. The patient contact reminds why I do this job and gives me the motivation to pursue the research. It’s a healthy balance for me and I can truly say that I love what I do for a living.

AC: Is there anything else you’d like to mention?

Dr. Modi: I would like to thank Conquer Cancer Foundation of ASCO and BCRF for supporting me and this research, and I hope we can continue to build forward from this project. Personally, I am most grateful for the guidance and support of my mentor, Dr. Clifford Hudis, who has been a tireless advocate and inspiration to me. I am thankful to all my collaborators, without whom this project could not have happened.

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Watch how CCF is working together with researchers to conquer breast cancer worldwide.