Research Summary

The overarching goal of my research is to improve treatment options and outcomes in patients with primary cancers of the liver and bile ducts through clinical and translational research of novel drugs and combinations along with biomarker analyses to identify the patients most likely to respond. My current work in hepatobiliary cancers includes leading multiple clinical trials of new immunotherapy treatment combinations, ranging from large, international phase 3 trials to smaller, investigator-initiated institutional trials with translational biomarker endpoints. I am also the PI of the UCSF Hepatobiliary Tissue Bank and Registry (HBTBR), initiated in 2012 to serve as a platform for translational and epidemiology research using fresh and archival tumor tissue samples, blood samples, and longitudinal clinical data from patients with hepatobiliary cancers who receive cancer care at UCSF. The HBTBR has enrolled over 500 cases since its activation in late 2012 and has contributed samples and data to multiple projects, including the NCI/NHGRI The Cancer Genome Atlas (TCGA) liver and cholangiocarcinoma cohorts, genome-wide association studies (GWAS) in HCC and cholangiocarcinoma, a University of California consortium project to develop minority patient-derived xenografts including hepatocellular carcinoma for tumor genomic analyses, the NCI's National Translational Science Network of Precision-Based Immunotherapy for Primary Liver Cancer, and many collaborative, retrospective studies of clinical outcomes.

Education

Harvard College, Boston, MA, B.A., 1993-97, Biochemistry
UCLA, M.D., 1998-2002, Medicine
UCLA, Intern, 2002-03, Medicine
UCLA, Resident, 2003-05, Medicine
UCLA, Chief Resident, 2005-06, Medicine
UCSF, Fellow, 2006-09, Hematology/Oncology

Honors & Awards

  • 1993-1997
    Harvard College Scholarship, Harvard College
  • 1993-1997
    Elizabeth Cary Agassiz Merit Award, Harvard College
  • 1997-1998
    Rotary Ambassadorial Scholarship, Costa Rica
  • 2001
    Alpha Omega Alpha, UCLA School of Medicine
  • 2001
    Merck Book Award, UCLA School of Medicine
  • 2001
    Janet M. Glascow Memorial Achievement Citation, American Medical Women's Association
  • 2004, 2006
    Solomon Scholars Resident Research Day Award, UCLA Department of Medicine
  • 2006
    Medical Student Teaching Award, UCLA Department of Medicine
  • 2009
    ASCO Cancer Foundation Merit Award, Gastrointestinal Cancers Symposium
  • 2010
    ASCO Young Investigator Award
  • 2014
    Cancer Clinical Investigator Team Leadership Award from the National Cancer Institute (NCI)

Selected Publications

  1. Song X, Kelley RK, Green M, Standifer N, Lim K, Zhou D, Dunyak J, Negro A, Kurland JF, Ren S, Khan AA, Gibbs M, Abou-Alfa GK. Modeling of Proliferating CD4 and CD8 T-Cell Changes to Tremelimumab Exposure in Patients with Unresectable Hepatocellular Carcinoma. Clin Pharmacol Ther. 2023 Oct; 114(4):874-882.  View on PubMed
  2. Spencer K, Pappas L, Baiev I, Maurer J, Bocobo AG, Zhang K, Jain A, De Armas AD, Reyes S, Le TM, Rahma OE, Stanton J, DeLeon TT, Roth M, Peters MLB, Zhu AX, Lennerz JK, Iafrate AJ, Boyhen K, VanCott C, Roberts LR, Lindsey S, Horick N, Goff LW, Mody K, Borad MJ, Shroff RT, Kelley RK, Javle MM, Goyal L. Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma. J Natl Cancer Inst. 2023 07 06; 115(7):870-880.  View on PubMed
  3. Budhu A, Pehrsson EC, He A, Goyal L, Kelley RK, Dang H, Xie C, Monge C, Tandon M, Ma L, Revsine M, Kuhlman L, Zhang K, Baiev I, Lamm R, Patel K, Kleiner DE, Hewitt SM, Tran B, Shetty J, Wu X, Zhao Y, Shen TW, Choudhari S, Kriga Y, Ylaya K, Warner AC, Edmondson EF, Forgues M, Greten TF, Wang XW. Tumor biology and immune infiltration define primary liver cancer subsets linked to overall survival after immunotherapy. Cell Rep Med. 2023 06 20; 4(6):101052.  View on PubMed
  4. Munson PV, Adamik J, Hartmann FJ, Favaro PMB, Ho D, Bendall SC, Combes AJ, Krummel MF, Zhang K, Kelley RK, Butterfield LH. Polyunsaturated Fatty Acid-Bound α-Fetoprotein Promotes Immune Suppression by Altering Human Dendritic Cell Metabolism. Cancer Res. 2023 05 02; 83(9):1543-1557.  View on PubMed
  5. Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klümpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A, KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 06 03; 401(10391):1853-1865.  View on PubMed
  6. Song X, Kelley RK, Khan AA, Standifer N, Zhou D, Lim K, Krishna R, Liu L, Wang K, McCoon P, Negro A, He P, Gibbs M, Kurland JF, Abou-Alfa GK. Exposure-Response Analyses of Tremelimumab Monotherapy or in Combination with Durvalumab in Patients with Unresectable Hepatocellular Carcinoma. Clin Cancer Res. 2023 02 16; 29(4):754-763.  View on PubMed
  7. Greten TF, Schwabe R, Bardeesy N, Ma L, Goyal L, Kelley RK, Wang XW. Immunology and immunotherapy of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 2023 06; 20(6):349-365.  View on PubMed
  8. Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, Kelley RK, Cassier PA, Klümpen HJ, Chang HM, Chen LT, Tabernero J, Oh DY, Mahipal A, Moehler M, Mitchell EP, Komatsu Y, Masuda K, Ahn D, Epstein RS, Halim AB, Fu Y, Salimi T, Wacheck V, He Y, Liu M, Benhadji KA, Bridgewater JA, FOENIX-CCA2 Study Investigators. Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. N Engl J Med. 2023 Jan 19; 388(3):228-239.  View on PubMed
  9. Kelley RK. The evolving role of combination systemic therapies in hepatocellular carcinoma. Clin Adv Hematol Oncol. 2022 Dec; 20(12):709-713.  View on PubMed
  10. McNamara MG, Bridgewater J, Goyal L, Jacobs T, Wagner AD, Goldstein D, Shroff R, Moehler M, Lowery M, Bekaii-Saab T, Kelley RK, Furuse J, Rimassa L, Morizane C, Lamarca A, Hubner R, Knox J, Valle J. What is the gender representation in authorship in later phase systemic clinical trials in biliary tract cancer (BTC)? - a retrospective review of the published literature. BMJ Open. 2022 10 26; 12(10):e064954.  View on PubMed
  11. Kelley RK. The Evolving Role of Combination Systemic Therapies in Hepatocellular Carcinoma. Gastroenterol Hepatol (N Y). 2022 Oct; 18(10):594-598.  View on PubMed
  12. Keenan BP, McCarthy EE, Ilano A, Yang H, Zhang L, Allaire K, Fan Z, Li T, Lee DS, Sun Y, Cheung A, Luong D, Chang H, Chen B, Marquez J, Sheldon B, Kelley RK, Ye CJ, Fong L. Circulating monocytes associated with anti-PD-1 resistance in human biliary cancer induce T cell paralysis. Cell Rep. 2022 09 20; 40(12):111384.  View on PubMed
  13. Zhu AX, Dayyani F, Yen CJ, Ren Z, Bai Y, Meng Z, Pan H, Dillon P, Mhatre SK, Gaillard VE, Hernandez S, Kelley RK, Sangro B. Alpha-Fetoprotein as a Potential Surrogate Biomarker for Atezolizumab + Bevacizumab Treatment of Hepatocellular Carcinoma. Clin Cancer Res. 2022 08 15; 28(16):3537-3545.  View on PubMed
  14. Kelley RK, Rimassa L, Cheng AL, Kaseb A, Qin S, Zhu AX, Chan SL, Melkadze T, Sukeepaisarnjaroen W, Breder V, Verset G, Gane E, Borbath I, Rangel JDG, Ryoo BY, Makharadze T, Merle P, Benzaghou F, Banerjee K, Hazra S, Fawcett J, Yau T. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 08; 23(8):995-1008.  View on PubMed
  15. Llovet JM, Pinyol R, Kelley RK, El-Khoueiry A, Reeves HL, Wang XW, Gores GJ, Villanueva A. Molecular pathogenesis and systemic therapies for hepatocellular carcinoma. Nat Cancer. 2022 04; 3(4):386-401.  View on PubMed
  16. Freemantle N, Mollon P, Meyer T, Cheng AL, El-Khoueiry AB, Kelley RK, Baron AD, Benzaghou F, Mangeshkar M, Abou-Alfa GK. Quality of life assessment of cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial. Eur J Cancer. 2022 06; 168:91-98.  View on PubMed
  17. El-Khoueiry AB, Meyer T, Cheng AL, Rimassa L, Sen S, Milwee S, Kelley RK, Abou-Alfa GK. Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to Child-Pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial. BMC Cancer. 2022 Apr 09; 22(1):377.  View on PubMed
  18. Falkson SR, Zhang K, Bhambhvani HP, Wild JL, Griffin A, Kelley RK, Gephart MH. Biliary cancer brain metastases: a multi-institution case series with case reports. J Gastrointest Oncol. 2022 Apr; 13(2):822-832.  View on PubMed
  19. Silverman IM, Li M, Murugesan K, Krook MA, Javle MM, Kelley RK, Borad MJ, Roychowdhury S, Meng W, Yilmazel B, Milbury C, Shewale S, Feliz L, Burn TC, Albacker LA. Validation and Characterization of FGFR2 Rearrangements in Cholangiocarcinoma with Comprehensive Genomic Profiling. J Mol Diagn. 2022 04; 24(4):351-364.  View on PubMed
  20. Burns S, Vella M, Paciorek A, Zhang L, Atreya CE, Feng M, Kelley RK, Tempero MA, Van Loon K, Ko AH. Characteristics and Growth Rate of Lung Metastases in Patients With Primary Gastrointestinal Malignancies and Lung-dominant Metastatic Disease: A Retrospective Cohort Analysis. Am J Clin Oncol. 2022 01 01; 45(1):22-27.  View on PubMed

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