Javier <span>F.</span> Torres-Roca, MD
Researcher

Javier F. Torres-Roca, MD

Academic Rank: Associate Member

Overview

The central interest of Dr. Torres-Roca’s laboratory is in the development of a systems level understanding of the biological networks that regulate radiosensitivity.

Discipline

    • Radiation Oncology
    • Chemical Biology and Molecular Medicine Program

Education & Training

    • University of Puerto Rico School of Medicine, MD
    • University of California, Irvine Medical Center, Resident - Radiation Oncology
    • Stanford University School of Medicine, Fellow - Genetics
    • Institut Pasteur, Fellow - Immunology
Research

The central interest of Dr. Torres-Roca’s laboratory is in the development of a systems level understanding of the biological networks that regulate radiosensitivity. We apply and integrate engineering principles and mathematical modeling along with experimental cellular and molecular biology in an effort to elucidate the topology and function of the radiosensitivity network. In collaboration with ET members (Eschrich SA and Chen DT) his group has developed a mathematical approach to integrate genomics, genotype, tissue type and biological pathway interactions to identify radiation-specific biomarkers in a large dataset of cancer cell lines. This strategy has resulted in the identification of a novel and highly redundant genetic free-scale network with 10 central nodes that we have proposed as central in the determination of radiophenotype.  We applied this knowledge by developing in cell lines a gene expression linear regression model of cellular radiosensitivity based on the expression of the ten central network hubs. This model was subsequently independently validated as a predictor of response and prognosis in 277 patients in four different disease sites (breast, head and neck, rectal, esophagus), thus providing critical clinical validation for this approach. An NCI-sponsored prospective clinical trial is currently underway at Moffitt to further test the systems-based gene expression model as a predictor of clinical response in rectal and esophageal cancer patients treated with preoperative concurrent chemoradiation. A major implication of this work is that mathematical modeling of cellular systems can lead to the development of technologies that can impact the clinic. Current efforts in the laboratory are aimed at integrating experimentally quantified cellular and clonogenic heterogeneity into computer-based virtual models of the clonogenic assay.

Publications

  • Strom T, Harrison LB, Giuliano AR, Schell MJ, Eschrich SA, Berglund A, Fulp W, Thapa R, Coppola D, Kim S, Frakes J, Foekens J, Mulé JJ, Torres-Roca JF. Tumour radiosensitivity is associated with immune activation in solid tumours. Eur J Cancer. 2017 Oct;84:304-314. Pubmedid: 28863385.
  • Scott JG, Harrison LB, Torres-Roca JF. Genomic biomarkers for precision radiation medicine - Authors' reply. Lancet Oncol. 2017 May;18(5):e239. Pubmedid: 28495285.
  • Caudell JJ, Torres-Roca JF, Gillies RJ, Enderling H, Kim S, Rishi A, Moros EG, Harrison LB. The future of personalised radiotherapy for head and neck cancer. Lancet Oncol. 2017 May;18(5):e266-e273. Pubmedid: 28456586.
  • Kamath VP, Torres-Roca JF, Eschrich SA. Integrating Biological Covariates into Gene Expression-Based Predictors of Radiation Sensitivity. Int J Genomics. 2017 Mar;2017:6576840. Pubmedid: 28280724. Pmcid: PMC5320380.
  • Scott JG, Harrison LB, Torres-Roca JF. Genomic-adjusted radiation dose - Authors' reply. Lancet Oncol. 2017 Mar;18(3):e129. Pubmedid: 28271862.
  • Hall WA, Bergom C, Thompson RF, Baschnagel AM, Vijayakumar S, Willers H, Li XA, Schultz CJ, Wilson GD, West CML, Capala J, Coleman CN, Torres-Roca JF, Weidhaas J, Feng FY. Precision Oncology and Genomically Guided Radiation Therapy: A Report From the American Society for Radiation Oncology/American Association of Physicists in Medicine/National Cancer Institute Precision Medicine Conference. Int J Radiat Oncol Biol Phys. 2017 Jun. Pubmedid: 28964588.
  • Strom T, Naghavi AO, Messina JL, Kim S, Torres-Roca JF, Russell J, Sondak VK, Padhya TA, Trotti AM, Caudell JJ, Harrison LB. Improved local and regional control with radiotherapy for Merkel cell carcinoma of the head and neck. Head Neck. 2017 Jan;39(1):48-55. Pubmedid: 27300153.
  • Scott JG, Berglund A, Schell MJ, Mihaylov I, Fulp WJ, Yue B, Welsh E, Caudell JJ, Ahmed K, Strom TS, Mellon E, Venkat P, Johnstone P, Foekens J, Lee J, Moros E, Dalton WS, Eschrich SA, McLeod H, Harrison LB, Torres-Roca JF. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol. 2017 Feb;18(2):202-211. Pubmedid: 27993569.
  • Ahmed KA, Berglund AE, Welsh EA, Naghavi AO, Kim Y, Yu M, Robinson TJ, Eschrich SA, Johnstone PA, Torres-Roca JF. The radiosensitivity of brain metastases based upon primary histology utilizing a multigene index of tumor radiosensitivity. Neurooncol. 2017 Aug;19(8):1145-1146. Pubmedid: 28379582. Pmcid: PMC5570253.
  • Strom T, Torres-Roca JF, Parekh A, Naghavi AO, Caudell JJ, Oliver DE, Messina JL, Khushalani NI, Zager JS, Sarnaik A, Mulé JJ, Trotti AM, Eschrich SA, Sondak VK, Harrison LB. Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma. J Natl Compr Canc Ne. 2017 Apr;15(4):473-482. Pubmedid: 28404758.
  • Ahmed KA, Strom T, Scott JG, Welsh EA, McLeod HL, Harrison LB, Eschrich SA, Torres-Roca JF. The Radiosensitivity Index (RSI) and the Connectivity Map: A Genomically Guided Approach for the Identification of Novel Radiosensitizers. Int J Radiat Oncol Biol Phys. 2016 Oct;96(2S):S236. Pubmedid: 27675869.
  • Parekh A, Strom T, Naghavi AO, Caudell JJ, Zager JS, Messina JL, Torres-Roca JF, Sondak VK, Trotti A, Harrison LB. Does Regional Radiation Therapy Impact Outcome for High-Risk, Node-Positive Cutaneous Melanoma?. Int J Radiat Oncol Biol Phys. 2016 Oct;96(2S):S157. Pubmedid: 27675666.
  • Strom T, Carr M, Zager JS, Naghavi A, Smith FO, Cruse CW, Messina JL, Russell J, Rao NG, Fulp W, Kim S, Torres-Roca JF, Padhya TA, Sondak VK, Trotti AM, Harrison LB, Caudell JJ. Radiation Therapy is Associated with Improved Outcomes in Merkel Cell Carcinoma. Ann Surg Oncol. 2016 Oct;23(11):3572-3578. Pubmedid: 27251134.
  • Ahmed KA, Berglund AE, Welsh EA, Naghavi AO, Perez BA, Dilling TJ, Eschrich SA, Torres-Roca JF. Differences in the Radiosensitivity Index (RSI) Between Lung Metastases Based Upon Primary Histology. Int J Radiat Oncol Biol Phys. 2016 Oct;96(2S):S68. Pubmedid: 27675988.
  • Grass GD, Teer J, Welsh EA, Eschrich SA, Torres-Roca JF. Multiscale Genomics to Model Functional Gene Networks Involved in Radiosensitivity. Int J Radiat Oncol Biol Phys. 2016 Oct;96(2S):E576. Pubmedid: 27675058.
  • Scott JG, Torres-Roca JF, Harrison LB, Berglund AE, Schell M, Mihaylov IB, Fulp WJ, Yue B, Welsh EA, Caudell JJ, Ahmed KA, Strom T, Mellon EA, Venkat PS, Johnstone PA, Moros EG, Lee J, Foekens J, Dalton WS, Eschrich SA, McLeod HL. A Genomic Framework for Precision Radiation Therapy. Int J Radiat Oncol Biol Phys. 2016 Oct;96(2S):S215-S216. Pubmedid: 27675815.
  • Ahmed KA, Torres-Roca JF. Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease. Cancer Control. 2016 Jan;23(1):21-29. Pubmedid: 27009453.
  • Gwede CK, Davis SN, Wilson S, Patel M, Vadaparampil ST, Meade CD, Rivers BM, Yu D, Torres-Roca J, Heysek R, Spiess PE, Pow-Sang J, Jacobsen P. Perceptions of Prostate Cancer Screening Controversy and Informed Decision Making: Implications for Development of a Targeted Decision Aid for Unaffected Male First-Degree Relatives. Am J Health Promot. 2016 Dec;29(6):393-401. Pubmedid: 24968183. Pmcid: PMC4277494.
  • Coit DG, Thompson JA, Algazi A, Andtbacka R, Bichakjian CK, Carson WE, Daniels GA, DiMaio D, Fields RC, Fleming MD, Gastman B, Gonzalez R, Guild V, Johnson D, Joseph RW, Lange JR, Martini MC, Materin MA, Olszanski AJ, Ott P, Gupta AP, Ross MI, Salama AK, Skitzki J, Swetter SM, Tanabe KK, Torres-Roca JF, Trisal V, Urist MM, McMillian N, Engh A. NCCN Guidelines Insights: Melanoma, Version 3.2016. J Natl Compr Canc Ne. 2016 Aug;14(8):945-958. Pubmedid: 27496110.
  • Ahmed KA, Caudell JJ, El-Haddad G, Berglund AE, Welsh EA, Yue B, Hoffe SE, Naghavi AO, Abuodeh YA, Frakes JM, Eschrich SA, Torres-Roca JF. Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys. 2016 Aug;95(5):1399-1404. Pubmedid: 27319288.
  • Coit DG, Thompson JA, Algazi A, Andtbacka R, Bichakjian CK, Carson WE, Daniels GA, DiMaio D, Ernstoff M, Fields RC, Fleming MD, Gonzalez R, Guild V, Halpern AC, Hodi FS, Joseph RW, Lange JR, Martini MC, Materin MA, Olszanski AJ, Ross MI, Salama AK, Skitzki J, Sosman J, Swetter SM, Tanabe KK, Torres-Roca JF, Trisal V, Urist MM, McMillian N, Engh A. Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Ne. 2016 Apr;14(4):450-473. Pubmedid: 27059193.
  • Strom T, Hoffe SE, Fulp W, Frakes J, Coppola D, Springett GM, Malafa MP, Harris CL, Eschrich SA, Torres-Roca JF, Shridhar R. Radiosensitivity index predicts for survival with adjuvant radiation in resectable pancreatic cancer. Radiother Oncol. 2015 Oct;117(1):159-164. Pubmedid: 26235848.
  • Ahmed KA, Chinnaiyan P, Fulp WJ, Eschrich S, Torres-Roca JF, Caudell JJ. The radiosensitivity index predicts for overall survival in glioblastoma. Oncotarget. 2015 Oct;6(33):34414-34422. Pubmedid: 26451615. Pmcid: PMC4741462.
  • Torres-Roca JF, Fulp WJ, Caudell JJ, Servant N, Bollet MA, van de Vijver M, Naghavi AO, Harris EE, Eschrich SA. Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer. Int J Radiat Oncol Biol Phys. 2015 Nov;93(3):631-638. Pubmedid: 26461005.
  • Ahmed KA, Fulp WJ, Berglund AE, Hoffe SE, Dilling TJ, Eschrich SA, Shridhar R, Torres-Roca JF. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection. Int J Radiat Oncol Biol Phys. 2015 Jul;92(4):837-842. Pubmedid: 25838188. Pmcid: PMC4481172.
  • Krauss DJ, Hu C, Bahary JP, Souhami L, Gore EM, Chafe SM, Leibenhaut MH, Narayan S, Torres-Roca J, Michalski J, Zeitzer KL, Donavanik V, Sandler H, McGowan DG, Jones CU, Shipley WU. Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients With Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408. Int J Radiat Oncol Biol Phys. 2015 Jul;92(4):863-873. Pubmedid: 26104939. Pmcid: PMC4480595.
  • Prokopiou S, Moros EG, Poleszczuk J, Caudell J, Torres-Roca JF, Latifi K, Lee JK, Myerson R, Harrison LB, Enderling H. A proliferation saturation index to predict radiation response and personalize radiotherapy fractionation. Radiat Oncol. 2015 Jul;10:159. Pubmedid: 26227259. Pmcid: PMC4521490.
  • Davis SN, Sutton SK, Vadaparampil ST, Meade CD, Rivers BM, Patel MV, Torres-Roca JF, Heysek RV, Spiess P, Pow-Sang J, Jacobsen PB, Gwede CK. Informed decision making among first-degree relatives of prostate cancer survivors: a pilot randomized trial. Contemp Clin Trials. 2014 Nov;39(2):327-334. Pubmedid: 25465497. Pmcid: PMC4274628.
  • Eschrich SA, Fulp WJ, Pawitan Y, Foekens JA, Smid M, Martens JW, Echevarria M, Kamath V, Lee JH, Harris EE, Bergh J, Torres-Roca JF. Validation of a radiosensitivity molecular signature in breast cancer. Clin Cancer Res. 2012 Sep;18(18):5134-5143. Pubmedid: 22832933. Pmcid: PMC3993974.
  • Torres-Roca JF. A molecular assay of tumor radiosensitivity: a roadmap towards biology-based personalized radiation therapy. Per Med. 2012 Jul;9(5):547-557. Pubmedid: 23105945. Pmcid: PMC3480204.
  • Finkelstein SE, Rodriguez F, Dunn M, Farmello MJ, Smilee R, Janssen W, Kang L, Chuang T, Seigne J, Pow-Sang J, Torres-Roca JF, Heysek R, Biagoli M, Shankar R, Scott J, Antonia S, Gabrilovich D, Fishman M. Serial assessment of lymphocytes and apoptosis in the prostate during coordinated intraprostatic dendritic cell injection and radiotherapy. Immunotherapy. 2012 Apr;4(4):373-382. Pubmedid: 22512631. Pmcid: PMC4241355.
  • Eschrich S, Zhang H, Zhao H, Boulware D, Lee JH, Bloom G, Torres-Roca JF. Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform. Int J Radiat Oncol Biol Phys. 2009 Oct;75(2):497-505. Pubmedid: 19735874. Pmcid: PMC2762403.
  • Eschrich SA, Pramana J, Zhang H, Zhao H, Boulware D, Lee JH, Bloom G, Rocha-Lima C, Kelley S, Calvin DP, Yeatman TJ, Begg AC, Torres-Roca JF. A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation. Int J Radiat Oncol Biol Phys. 2009 Oct;75(2):489-496. Pubmedid: 19735873. Pmcid: PMC3038688.
  • Torres-Roca J, Stevens C. Predicting response to clinical radiotherapy: past, present, and future directions. Cancer Control. 2008 Apr;15(2):151-156. Pubmedid: 18376382.
  • Scuto A, Zhang H, Zhao H, Rivera M, Yeatman TJ, Jove R, Torres-Roca JF. RbAp48 regulates cytoskeletal organization and morphology by increasing K-Rasactivity and signaling through mitogen-activated protein kinase. Cancer Res. 2007 Nov;67(21):10317-10324. Pubmedid: 17974974.
  • Torres-Roca J, DeSilvio M, Mora L, Khor L, Hammond E, Ahmad N, Jove R, Forman J, Lee R, Sandler H, Pollack A. Activated STAT3 as a correlate of distant metastasis in prostate cancer: a secondary analysis of Radiation Therapy Oncology Group 86-10. Urology. 2007 Mar;69(3):505-509. Pubmedid: 17382154.
  • Torres-Roca JF, Cantor AB, Shukla S, Montejo ME, Friedland J, Seigne JD, Heysek R, Heysek, Randy, Pow-Sang J. Treatment of intermediate-risk prostate cancer with brachytherapy without supplemental pelvic radiotherapy: a review of the H. Lee Moffitt Cancer Center experience. Urol Oncol. 2006 Sep;24(5):384-390. Pubmedid: 16962486.
  • Torres-Roca J, Cantor A, Shukla S, Montejo M, Friedland J, Seigne J, Heysek R, Pow-Sang J. Treatment of intermediate-risk prostate cancer with brachytherapy without supplemental pelvic radiotherapy: a review of the H. Lee Moffitt Cancer Center experience. Urol Oncol. 2006 Oct;24(5):384-390. Pubmedid: 16962486.
  • Torres-Roca J. The role of external-beam radiation therapy in the treatment of clinicallylocalized prostate cancer. Cancer Control. 2006 Jul;13(3):188-193. Pubmedid: 16885914.
  • Torres-Roca JF, Eschrich S, Zhao H, Bloom G, Sung J, McCarthy S, Cantor AB, Scuto A, Li C, Zhang S, Jove R, Yeatman T. Prediction of radiation sensitivity using a gene expression classifier. Cancer Res. 2005 Aug;65(16):7169-7176. Pubmedid: 16103067.
  • Torres-Roca J. Bladder preservation protocols in the treatment of muscle-invasive bladder cancer. Cancer Control. 2004;11(6):358-363. Pubmedid: 15625523.
  • Calvin D, Nam S, Buettner R, Sekharam M, Torres-Roca J, Jove R. Inhibition of STAT3 activity with STAT3 antisense oligonucleotide (STAT3-ASO) enhances radiation-induced apoptosis in DU145 prostate cancer cells. Int J Radiat Oncol Biol Phys. 2003;57:S297-S297. Pubmedid: 12965611.
  • Katsikis PD, Garcia-Ojeda ME, Torres-Roca JF, Tijoe IM, Smith CA, Herzenberg LA, Herzenberg LA. Interleukin-1 beta converting enzyme-like protease involvement in Fas-induced and activation-induced peripheral blood T cell apoptosis in HIV infection. TNF-related apoptosis-inducing ligand can mediate activation-induced T cell death in HIV infection. J Exp Med. 1997 Oct;186(8):1365-1372. Pubmedid: 9334376. Pmcid: PMC2199088.
  • Heysek R, Gwede C, Torres-Roca J, Cantor A, Kelley S, Saini A, Pow-Sang J. A dosimetric analysis of unstranded seeds versus customized stranded seeds in transperineal interstitial permanent prostate seed brachytherapy. Brachytherapy. 5(4):244-250. Pubmedid: 17118318.