Bio


Robert W. Hsieh, M.D. Ph.D. is a medical oncologist who specializes in the treatment of prostate cancer, bladder cancer, kidney (renal) cancer and testicular cancer as a member of Stanford's multi-disciplinary Urologic Cancer Program. Dr. Hsieh obtained his M.D. and Ph.D. degrees at the University of Chicago (Pritzker School of Medicine) and subsequently came to Stanford to complete his Internal Medicine residency and Hematology and Oncology fellowship training (with a clinical focus on genitourinary cancers).

Dr. Hsieh has also had extensive experience in basic lab research (cancer stem cells, target identification and validation, pre-clinical drug discovery) having done post-doctoral work in the Clarke Lab in the Institute for Stem Cell Biology and Regenerative Medicine. He is currently involved in early phase clinical trials in immuno-oncology in industry.

Clinical Focus


  • Genitourinary Oncology
  • Prostate Cancer
  • Kidney (Renal) Cancer
  • Bladder Cancer
  • Testicular Cancer
  • Medical Oncology

Honors & Awards


  • Project Grant (co-Principal Investigator), SPARK Translational Research Program (2018)
  • Fellowship Award, Stanford Cancer Institute (2015-2016)
  • Scholar Award, California Institute of Regenerative Medicine (CIRM) (2015-2016)
  • Fellows Recognition Award, National Comprehensive Cancer Network (NCCN) (2013)
  • The Leon O. Jacobson Basic Science Prize, The University of Chicago (2009)
  • Frank Family Fellowship, The University of Chicago (2006-2009)
  • Medical Scientist Training Program Award (MSTP), The University of Chicago (2001-2009)

Boards, Advisory Committees, Professional Organizations


  • Medical Oncology Board Certification, American Board of Internal Medicine (2016 - Present)
  • Internal Medicine Board Certification, American Board of Internal Medicine (2012 - Present)

Professional Education


  • Board Certification: American Board of Internal Medicine, Medical Oncology (2016)
  • Fellowship: Stanford University Hematology and Oncology Fellowship (2016) CA
  • Residency: Stanford University Internal Medicine Residency (2011) CA
  • Internship, Stanford University, Internal Medicine (2010)
  • M.D., The University of Chicago, Medicine (2009)
  • Ph.D., The University of Chicago, Biochemistry and Molecular Biology (2006)
  • B.S., Stanford University, Electrical Engineering and Biological Sciences (2001)

Patents


  • Robert W Hsieh. "United StatesCDK19"

Graduate and Fellowship Programs


All Publications


  • Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. The Lancet. Oncology Cho, B. C., Abreu, D. R., Hussein, M., Cobo, M., Patel, A. J., Secen, N., Lee, K. H., Massuti, B., Hiret, S., Yang, J. C., Barlesi, F., Lee, D. H., Ares, L. P., Hsieh, R. W., Patil, N. S., Twomey, P., Yang, X., Meng, R., Johnson, M. L. 2022

    Abstract

    Targeted inhibition of the PD-L1-PD-1 pathway might be further amplified through combination of PD-1 or PD-L1 inhibitors with novel anti-TIGIT inhibitory immune checkpoint agents, such as tiragolumab. In the CITYSCAPE trial, we aimed to assess the preliminary efficacy and safety of tiragolumab plus atezolizumab (anti-PD-L1) therapy as first-line treatment for non-small-cell lung cancer (NSCLC).CITYSCAPE is a phase 2, randomised, double-blind, placebo-controlled trial. Patients with chemotherapy-naive, PD-L1-positive (defined as a tumour proportion score of ≥1% by 22C3 immunohistochemistry pharmDx assay; Dako, Agilent Technologies, Santa Clara, CA, USA) recurrent or metastatic NSCLC with measurable disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and no EGFR or ALK alterations were enrolled from 41 clinics in Europe, Asia, and the USA. Patients were randomly assigned (1:1), via an interactive voice or web-based response system, to receive tiragolumab (600 mg) plus atezolizumab (1200 mg) or placebo plus atezolizumab intravenously once every 3 weeks. Investigators and patients were masked to treatment assignment. The co-primary endpoints were investigator-assessed objective response rate and progression-free survival as per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population, analysed after approximately 80 progression-free survival events had been observed in the primary population. Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03563716, and is ongoing.Patients were enrolled between Aug 10, 2018, and March 20, 2019. At data cutoff for the primary analysis (June 30, 2019), 135 of 275 patients assessed for eligibility were randomly assigned to receive tiragolumab plus atezolizumab (67 [50%]) or placebo plus atezolizumab (68 [50%]). In this primary analysis, after a median follow-up of 5·9 months (4·6-7·6, in the intention-to-treat population, 21 patients (31·3% [95% CI 19·5-43·2]) in the tiragolumab plus atezolizumab group versus 11 patients (16·2% [6·7-25·7]) in the placebo plus atezolizumab group had an objective response (p=0·031). Median progression-free survival was 5·4 months (95% CI 4·2-not estimable) in the tiragolumab plus atezolizumab group versus 3·6 months (2·7-4·4) in the placebo plus atezolizumab group (stratified hazard ratio 0·57 [95% CI 0·37-0·90], p=0·015). 14 (21%) patients receiving tiragolumab plus atezolizumab and 12 (18%) patients receiving placebo plus atezolizumab had serious treatment-related adverse events. The most frequently reported grade 3 or worse treatment-related adverse event was lipase increase (in six [9%] patients in the tiragolumab plus atezolizumab group vs two [3%] in the placebo plus atezolizumab group). Two treatment-related deaths (of pyrexia and infection) occurred in the tiragolumab plus atezolizumab group.Tiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1-positive, recurrent or metastatic NSCLC. Tiragolumab plus atezolizumab was well tolerated, with a safety profile generally similar to that of atezolizumab alone. These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC.F Hoffmann-La Roche and Genentech.

    View details for DOI 10.1016/S1470-2045(22)00226-1

    View details for PubMedID 35576957

  • Implementation of a cloud-based electronic patient-reported outcome (ePRO) platform in patients with advanced cancer. Journal of patient-reported outcomes Generalova, O., Roy, M., Hall, E., Shah, S. A., Cunanan, K., Fardeen, T., Velazquez, B., Chu, G., Bruzzone, B., Cabot, A., Fisher, G. A., Srinivas, S., Fan, A. C., Haraldsdottir, S., Wakelee, H. A., Neal, J. W., Padda, S. K., Johnson, T., Heestand, G. M., Hsieh, R. W., Ramchandran, K. 2021; 5 (1): 91

    Abstract

    BACKGROUND: Patient reported outcomes (PROs) have been associated with improved symptom management and quality of life in patients with cancer. However, the implementation of PROs in an academic clinical practice has not been thoroughly described. Here we report on the execution, feasibility and healthcare utilization outcomes of an electronic PRO (ePRO) application for cancer patients at an academic medical center.METHODS: We conducted a randomized trial comparing an experimental ePRO arm to standard of care in patients with advanced cancer in the thoracic, gastrointestinal, and genitourinary oncology groups at Stanford Cancer Center from March 2018 to November 2019. We describe the pre-implementation, implementation, and post-implementation phases of the ePRO arm, technological barriers, electronic health record (EHR) integration, clinician burden, and patient data privacy and security. Feasibility was pre-specified to be at least 70% completion of all questionnaires. Acceptability was based on patient and clinician feedback. Ambulatory healthcare utilization was assessed by reviewing numbers of phone messages, electronic portal messages, and referrals for supportive care.RESULTS: Of 617 ePRO questionnaires sent to 72 patients, 445 (72%) were completed. Most clinicians (87.5%) and patients (93%) felt neutral or positive about the ePRO tool's ease of use. Exposure to ePRO did not cause a measurable change in ambulatory healthcare utilization, with a median of less than two phone messages and supportive care referrals, and 5-6 portal messages.CONCLUSIONS: Web-based ePRO tools for patients with advanced cancer are feasible and acceptable without increasing clinical burden. Key lessons include the importance of pilot testing, engagement of stakeholders at all levels, and the need for customization by disease group. Future directions for this work include completion of EHR integration, expansion to other centers, and development of integrated workflows for routine clinical practice.

    View details for DOI 10.1186/s41687-021-00358-2

    View details for PubMedID 34524558

  • Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors Bendell, J. C., Bedard, P., Bang, Y., LoRusso, P., Hodi, S., Gordon, M., D'Angelo, S., Desai, J., Garralda, E., Italiano, A., Myung-Ju Ahn, Cervantes, A., Wainberg, Z., Calvo, E., Gil-Martin, M., Martinez-Garcia, M., Bahleda, R., Cassier, P., Delord, J., Prawira, A., Melero, I., Emens, L., Romano, E., Miller, K., Hsieh, R. W., Xue, C., Morrissey, K., Twomey, P., Gash, K., Patil, N. S., Grogan, J., Meng, R., Cho, B., Kim, T. AMER ASSOC CANCER RESEARCH. 2020
  • Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE). Rodriguez-Abreu, D., Johnson, M., Hussein, M. A., Cobo, M., Patel, A., Secen, N., Lee, K., Massuti, B., Hiret, S., Yang, J., Barlesi, F., Lee, D., Paz-Ares, L. G., Hsieh, R., Miller, K., Patil, N., Twomey, P., Kapp, A., Meng, R., Cho, B. AMER SOC CLINICAL ONCOLOGY. 2020
  • Single-cell transcriptional diversity is a hallmark of developmental potential. Science (New York, N.Y.) Gulati, G. S., Sikandar, S. S., Wesche, D. J., Manjunath, A. n., Bharadwaj, A. n., Berger, M. J., Ilagan, F. n., Kuo, A. H., Hsieh, R. W., Cai, S. n., Zabala, M. n., Scheeren, F. A., Lobo, N. A., Qian, D. n., Yu, F. B., Dirbas, F. M., Clarke, M. F., Newman, A. M. 2020; 367 (6476): 405–11

    Abstract

    Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation is challenging. Here, we demonstrate a simple, yet robust, determinant of developmental potential-the number of expressed genes per cell-and leverage this measure of transcriptional diversity to develop a computational framework (CytoTRACE) for predicting differentiation states from scRNA-seq data. When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. This study thus establishes a key RNA-based feature of developmental potential and a platform for delineation of cellular hierarchies.

    View details for DOI 10.1126/science.aax0249

    View details for PubMedID 31974247

  • Role of epithelial to mesenchymal transition associated genes in mammary gland regeneration and breast tumorigenesis. Nature communications Sikandar, S. S., Kuo, A. H., Kalisky, T. n., Cai, S. n., Zabala, M. n., Hsieh, R. W., Lobo, N. A., Scheeren, F. A., Sim, S. n., Qian, D. n., Dirbas, F. M., Somlo, G. n., Quake, S. R., Clarke, M. F. 2017; 8 (1): 1669

    Abstract

    Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts we demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of EMT-associated genes. In breast cancer, while a subset of cells with epithelial and mesenchymal phenotypes have stem cell activity, in many cells that have lost epithelial characteristics with increased expression of mesenchymal genes, have decreased tumor-initiating capacity and plasticity. These findings have implications for the development of effective therapeutic agents targeting tumor-initiating cells.

    View details for PubMedID 29162812

    View details for PubMedCentralID PMC5698470

  • Cryptococcal osteomyelitis and meningitis in a patient with non-hodgkin's lymphoma treated with PEP-C. BMJ case reports To, C. A., Hsieh, R. W., McClellan, J. S., Howard, W., Fischbein, N. J., Brown, J. M., Felsher, D. W., Fan, A. C. 2012; 2012

    Abstract

    The authors present the first case report of a patient with lymphoma who developed disseminated cryptococcal osteomyelitis and meningitis while being treated with the PEP-C (prednisone, etoposide, procarbazine and cyclophosphamide) chemotherapy regimen. During investigation of fever and new bony lesions, fungal culture from a rib biopsy revealed that the patient had cryptococcal osteomyelitis. Further evaluation demonstrated concurrent cryptococcal meningitis. The patient's disseminated cryptococcal infections completely resolved after a full course of antifungal treatment. Cryptococcal osteomyelitis is itself an extremely rare diagnosis, and the unique presentation with concurrent cryptococcal meningitis in our patient with lymphoma was likely due to his PEP-C treatment. It is well recognised that prolonged intensive chemotherapeutic regimens place patients at risk for atypical infections; yet physicians should recognise that even chronic low-dose therapies can put patients at risk for fungal infections. Physicians should consider fungal infections as part of the infectious investigation of a lymphopaenic patient on PEP-C.

    View details for DOI 10.1136/bcr.08.2011.4578

    View details for PubMedID 22962380

  • Molecular characterization of a B-ring unsaturated estrogen: Implications for conjugated equine estrogen components of Premarin STEROIDS Hsieh, R. W., Rajan, S. S., Sharma, S. K., Greene, G. L. 2008; 73 (1): 59-68

    Abstract

    Conjugated equine estrogens (CEEs) are routinely used for hormone replacement therapy (HRT), making it important to understand the activities of individual estrogenic components. Although 17beta-estradiol (17beta-E2), the most potent estrogen in CEE, has been extensively characterized, the actions of nine additional less potent estrogens are not well understood. Structural differences between CEEs and 17beta-E2 result in altered interactions with the two estrogen receptors (ERalpha and ERbeta) and different biological activities. To better understand these interactions, we have determined the crystal structure of the CEE analog, 17beta-methyl-17alpha-dihydroequilenin (NCI 122), in complex with the ERalpha ligand-binding domain and a peptide from the glucocorticoid receptor-interacting protein 1 (GRIP1) coactivator. NCI 122 has chemical properties, including an unsaturated B-ring and 17alpha-hydroxyl group, which are shared with some of the estrogens found in CEEs. Structural analysis of the NCI 122-ERalpha LBD-GRIP1 complex, combined with biochemical and cell-based comparisons of CEE components, suggests that factors such as decreased ligand flexibility, decreased ligand hydrophobicity and loss of a hydrogen bond between the 17-hydroxyl group and His524, contribute significantly to the reduced potency of CEEs on ERalpha.

    View details for DOI 10.1016/j.ste.roids.2007.08.014

    View details for Web of Science ID 000252602600007

    View details for PubMedID 17949766

  • Identification of ligands with bicyclic scaffolds provides insights into mechanisms of estrogen receptor subtype selectivity JOURNAL OF BIOLOGICAL CHEMISTRY Hsieh, R. W., Rajan, S. S., Sharma, S. K., Guo, Y., DeSombre, E. R., Mrksich, M., Greene, G. L. 2006; 281 (26): 17909-17919

    Abstract

    Estrogen receptors alpha (ERalpha) and beta (ERbeta) have distinct functions and differential expression in certain tissues. These differences have stimulated the search for subtype-selective ligands. Therapeutically, such ligands offer the potential to target specific tissues or pathways regulated by one receptor subtype without affecting the other. As reagents, they can be utilized to probe the physiological functions of the ER subtypes to provide information complementary to that obtained from knock-out animals. A fluorescence resonance energy transfer-based assay was used to screen a 10,000-compound chemical library for ER agonists. From the screen, we identified a family of ERbeta-selective agonists whose members contain bulky oxabicyclic scaffolds in place of the planar scaffolds common to most ER ligands. These agonists are 10-50-fold selective for ERbeta in competitive binding assays and up to 60-fold selective in transactivation assays. The weak uterotrophic activity of these ligands in immature rats and their ability to stimulate expression of an ERbeta regulated gene in human U2OS osteosarcoma cells provides more physiological evidence of their ERbeta-selective nature. To provide insight into the molecular mechanisms of their activity and selectivity, we determined the crystal structures of the ERalpha ligand-binding domain (LBD) and a peptide from the glucocorticoid receptor-interacting protein 1 (GRIP1) coactivator complexed with the ligands OBCP-3M, OBCP-2M, and OBCP-1M. These structures illustrate how the bicyclic scaffolds of these ligands are accommodated in the flexible ligand-binding pocket of ER. A comparison of these structures with existing ER structures suggests that the ERbeta selectivity of OBCP ligands can be attributed to a combination of their interactions with Met-336 in ERbeta and Met-421 in ERalpha. These bicyclic ligands show promise as lead compounds that can target ERbeta. In addition, our understanding of the molecular determinants of their subtype selectivity provides a useful starting point for developing other ER modulators belonging to this relatively new structural class.

    View details for DOI 10.1074/jbc.M513684200

    View details for Web of Science ID 000238490300041

    View details for PubMedID 16648639

  • Label-free detection of protein-protein interactions on biochips ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Yeo, W. S., Min, D. H., Hsieh, R. W., GREENE, G. L., Mrksich, M. 2005; 44 (34): 5480-5483

    View details for DOI 10.1002/anie.200501363

    View details for Web of Science ID 000231639400016

    View details for PubMedID 16052641

  • Interdigital cantilever as a biological sensor 1st IEEE Conference on Nanotechnology (IEEE-NANO 2001) Sulchek, T., Hsieh, R., Minne, S. C., Quate, C. F., Manalis, S. R. IEEE. 2001: 562–566
  • High-speed atomic force microscopy in liquid REVIEW OF SCIENTIFIC INSTRUMENTS Sulchek, T., Hsieh, R., Adams, J. D., Minne, S. C., Quate, C. F., Adderton, D. M. 2000; 71 (5): 2097-2099
  • High-speed tapping mode imaging with active Q control for atomic force microscopy APPLIED PHYSICS LETTERS Sulchek, T., Hsieh, R., Adams, J. D., Yaralioglu, G. G., Minne, S. C., Quate, C. F., Cleveland, J. P., Atalar, A., Adderton, D. M. 2000; 76 (11): 1473-1475