David T. Miyamoto, MD, PhD
Assistant Professor of Radiation Oncology
Harvard Medical School
Massachusetts General Hospital Cancer Center
Center for Cancer Research
Explore the Miyamoto Lab
The Miyamoto laboratory focuses on the discovery and development of novel biomarkers to guide the personalized treatment of patients with prostate and bladder cancer. We focus on two general classes of biomarkers, namely those based on the molecular profiles of tumor biopsies, and those based on circulating tumors cells (CTCs) in the blood that can be sampled noninvasively and repeatedly. By analyzing these patient-derived specimens, we have identified new molecular predictors of response to therapy and potential mechanisms of treatment resistance. Our overall aim is to develop tools for “realtime precision medicine” to probe the molecular signatures of cancers as they evolve over time, and to guide the precise and rational selection of appropriate therapies for each individual patient with prostate or bladder cancer.
The mission of our translational research laboratory is to discover and develop molecular biomarkers that inform clinical decisions in the management of patients with genitourinary malignancies. We aim to develop circulating and tissue-based biomarkers in a variety of clinical contexts in order to actualize the concept “real-time precision medicine”, integrating genomic analyses of liquid and tissue biopsies to guide the personalized care of patients with genitourinary malignancies.
Prostate cancer is the most common cancer in men and the second leading cause of cancer-related death in men. There is a critical unmet need for predictive biomarkers to guide prostate cancer therapy in settings ranging from localized to metastatic disease. In localized prostate cancer, reliable biomarkers are sorely needed to guide the rational selection of appropriate management options tailored to each patient’s tumor, including active surveillance, radical prostatectomy, or radiation therapy. In metastatic prostate cancer, multiple FDA-approved therapeutic options that increase survival are now available, including androgen receptor (AR) targeted therapies, cytotoxic chemotherapy, and PARP inhibitors. However, we lack non-invasive biomarkers that can reliably predict treatment responses and precisely guide selection of the most appropriate therapy for each individual patient. A major focus of our laboratory is the investigation of circulating tumors cells (CTCs), which are rare cancer cells shed from primary and metastatic tumors into the peripheral blood. CTCs represent a type of “liquid biopsy” that may be performed repeatedly and noninvasively to monitor treatment efficacy and study tumor evolution during therapy. In collaboration with a multidisciplinary team at MGH, we have developed novel molecular assays using microfluidic technologies to isolate and analyze CTCs from the blood of cancer patients. Our recent studies include the interrogation of androgen receptor (AR) signaling status to predict therapeutic response in patients receiving AR-targeted therapies, and the use of single cell RNA-seq to nominate noncanonical Wnt signaling as a contributor to enzalutamide resistance. Most recently, we derived CTC RNA signatures that predict resistance to AR-targeted therapy in metastatic cancer and early dissemination in localized cancer. Ongoing projects include the development of CTC molecular signatures for the prediction of clinical outcomes after radiation therapy, and for the early detection of clinically significant prostate cancer. Another focus of the laboratory is the development of novel tissue-based biomarkers. We utilize technologies including microfluidic real-time PCR, next-generation sequencing, and RNA in situ hybridization (RNA-ISH) to evaluate molecular signatures in limited quantities of tumor biopsy tissues. Our past and ongoing efforts are directed at correlating molecular findings with clinical outcomes in order to identify novel biomarkers predictive of treatment response.
Bladder cancer is the fifth most common cancer in the US, causing 18,000 deaths per year. Muscle-invasive bladder cancer is aggressive and has a high propensity for metastasis, but can often be treated effectively with either radical cystectomy or bladder-sparing trimodality therapy (transurethral tumor resection followed by chemoradiation). However, the decision regarding which treatment to pursue is often made based on arbitrary factors including patient or physician preference. There is an urgent unmet need for molecular biomarkers to guide patients towards the most appropriate therapy based on the biology of their tumor. We recently performed gene expression profiling of bladder tumors from patients treated with bladder preservation therapy, and identified immune and stromal molecular signatures predictive of outcomes after chemoradiation therapy. We are currently evaluating these and other candidate biomarkers as predictors of treatment response in prospective clinical trials and carefully defined retrospective clinical cohorts.
Efstathiou JA, Mouw K, Gibb E, Liu Y, Wu CL, Drumm M, da Costa JB, du Plessis M, Wang NQ, Davicioni E, Feng FY, Seiler R, Black PC, Shipley WU, Miyamoto DT. Impact of immune and stromal infiltration on outcomes following bladder-sparing trimodality therapy for muscle-invasive bladder cancer. European Urology. 2019; 76:59-68.
Miyamoto DT, Lee RJ, Kalinich M, LiCausi J, Zheng Y, Chen T, Milner JD, Emmons E, Ho U, Broderick K, Silva E, Javaid S, Kwan TT, Hong X, Dahl DM, McGovern FJ, Efstathiou JA, Smith MR, Sequist LV, Kapur R, Wu CL, Stott SL, Ting DT, Giobbie- Hurder A, Toner M, Maheswaran S, Haber DA. An RNA-based digital circulating tumor cell signature is predictive of drug response and early dissemination in prostate cancer. Cancer Discovery. 2018; 8:288-303.
Miyamoto DT, et. al. Molecular biomarkers in bladder preservation therapy for muscle-invasive bladder cancer. Lancet Oncology. 2018; 19:e683-e695.
Saylor PJ, Lee RJ, Arora KS, Deshpande V, Hu R, Olivier K, Meneely E, Rivera MN, Ting DT, Wu CL, Miyamoto DT. Branched chain RNA in situ hybridization for androgen receptor splice variant AR-V7 as a prognostic biomarker for metastatic castration-sensitive prostate cancer. Clinical Cancer Research. 2017; 23:363-369.
Zheng Y*, Miyamoto DT*, Wittner BS, Sullivan JP, Aceto N, Jordan NV, Yu M, Karabacak NM, Comaills V, Morris R, Desai R, Desai N, Emmons E, Lee RJ, Wu CL, Sequist LV, Haas W, Ting DT, Toner M, Ramaswamy S, Maheswaran S, Haber DA. Expression of ß-globin by cancer cells promotes cell survival during dissemination. Nature Communications. 2017; 8:14344.
Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT, Desai R, Fox DB, Brannigan BW, Trautwein J, Arora KS, Desai N, Dahl DM, Sequist LV, Smith MR, Kapur R, Wu CL, Shioda T, Ramaswamy S, Ting DT, Toner M, Maheswaran S, Haber DA. RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science. 2015; 349:1351-1356.
* Co-first authors
A dividing circulating tumor cell isolated from a prostate cancer patient, immunostained for PSA (red), PSMA (orange), and DNA (blue), adjacent to a leukocyte immunostained for CD45 (green) and DNA (blue).
Learn more about the people working in our lab.
- Assistant Professor of Radiation Oncology, Harvard Medical School
- Rebecca Fisher, RN
- William Hwang, MD, PhD
- Erika Kusaka, BA
- Keisuke Otani, MD, PhD
- Haley Pleskow, BA
- Jacob Ukleja, BS
- Qingyuan “Emma” Yang, PhD