Clinical Trial Keywords:
immunotherapy, vaccine, pancreas cancer, pancreatic cancer
In collaboration with Dr. Elizabeth Jaffee, he has developed clinical studies to optimize an immune therapy approach using GM-CSF transfected pancreatic cell lines as a vaccine in two distinct patient populations. First, the vaccine has been integrated with chemotherapy and radiation therapy in patients with resected pancreatic cancer who are at risk for disease recurrence. Second, the vaccine has been integrated with novel molecular targeted drugs such as EGFR inhibitors and anti-CTLA-4 antibody and with immune modulating doses of Cytoxan in patients with metastatic pancreatic cancer. He has also incorporated correlative studies that should provide important information to better understand optimal vaccine boosting schedules as well as to identify antigens that can be predictive markers for anti-pancreatic cancer immune responses.
In collaboration with Dr. Chris Iacobuzio-Donahue, he is investigating mechanisms of chemotherapy resistance in pancreatic cancer. In collaboration with Dr. Anirban Maitra and Dr. William Matsui he is investigating small molecule drugs that target pancreatic cancer growth and pancreatic stroma pathways and pancreatic cancer progenitor cells. In collaboration with Dr. Joe Herman in Radiation Oncology as well as Drs. John Cameron, Rich Schulick, Barish Edil, Chris Wolfgang, Tim Pawlik, Mike Choti in Surgical Oncology, he is testing new therapies in resectable and locally advanced pancreatic cancer.
In collaboration with Dr. Chi Dang, he is developing new targets that inhibit cancer metabolism.
Herman, J.M., Swartz, M.J., Hsu, C.C., Winter, J., Pawlik, T.M., Sugar, E., Robinson, R., Laheru, D.A., Jaffee, E., Hruban, R.H., Campbell, K.A., Wolfgang, C.L., Asrari, F., Donehower, R., Hidalgo, M., Diaz, L.A., Jr., Yeo, C., Cameron, J.L., Schulick, R.D., and Abrams, R. (2008). Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol 26, 3503-3510.
Jimeno, A., Li, J., Messersmith, W.A., Laheru, D., Rudek, M.A., Maniar, M., Hidalgo, M., Baker, S.D., and Donehower, R.C. (2008). Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol 26, 5504-5510.
Jimeno, A., Messersmith, W.A., Lee, C.K., Ma, W.W., Laheru, D., Donehower, R.C., Baker, S.D., and Hidalgo, M. (2008). Phase I study of troxacitabine administered by continuous infusion in subjects with advanced solid malignancies. Ann Oncol 19, 374-379.
Jimeno, A., Rudek, M.A., Kulesza, P., Ma, W.W., Wheelhouse, J., Howard, A., Khan, Y., Zhao, M., Jacene, H., Messersmith, W.A., Laheru, D., Donehower, R.C., Garrett-Mayer, E., Baker, S.D., and Hidalgo, M. (2008).
Pharmacodynamic-guided modified continuous reassessment method-based, dose-finding study of rapamycin in adult patients with solid tumors. J Clin Oncol 26, 4172-4179.
Laheru, D. & Yeo, C. J. (2005). Role of adjuvant therapy in the management of pancreatic cancer. Adv Surg 39, 223-44.
Laheru, D. A., Pardoll, D. M. & Jaffee, E. M. (2005). Genes to vaccines for immunotherapy: how the molecular biology revolution has influenced cancer immunology. Mol Cancer Ther 4, 1645-52.
Laheru, D., Biedrzycki, B., Thomas, A. M. & Jaffee, E. M. (2005). Development of a cytokine-modified allogeneic whole cell pancreatic cancer vaccine. Methods Mol Med 103, 299-327.
Laheru, D., Croghan, G., Bukowski, R., Rudek, M., Messersmith, W., Erlichman, C., Pelley, R., Jimeno, A., Donehower, R., Boni, J., Abbas, R., Martins, P., Zacharchuk, C., and Hidalgo, M. (2008). A phase I study of EKB-569 in combination with capecitabine in patients with advanced colorectal cancer. Clin Cancer Res 14, 5602-5609.
Laheru, D., Lutz, E., Burke, J., Biedrzycki, B., Solt, S., Onners, B., Tartakovsky, I., Nemunaitis, J., Le, D., Sugar, E., Hege, K., and Jaffee, E. (2008). Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res 14, 1455-1463.
Sebastiani, V., Ricci, F., Rubio-Viquiera, B., Kulesza, P., Yeo, C. J., Hidalgo, M., Klein, A., Laheru, D. & Iacobuzio-Donahue, C. A. (2006). Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res 12, 2492-7.
Swartz, M. J., M. A. Hughes, D. A. Frassica, J. Herman, C. J. Yeo, T. S. Riall, K. D. Lillemoe, J. L. Cameron, R. C. Donehower, D. A. Laheru, R. H. Hruban, and R. A. Abrams. 2007. Adjuvant concurrent chemoradiation for node-positive adenocarcinoma of the duodenum. Arch Surg 142:285-8.
Laheru, D. A., Pardoll, D. M., & Jaffee, E. M. 2005. Genes to vaccines for immunotherapy: how the molecular biology revolution has influenced cancer immunology. Mol. Cancer Ther. 4:1645-1652.
Laheru, D. A., & Jaffee, E. M. 2005. Immunotherapy for pancreatic cancer: science driving clinical progress. [Review]. Nat. Rev. Cancer. 5:459-467.
Iacobuzio-Donahue C, Fu B, Yachida S, Luo M, Abe H, Henderson CM, Vilardell F, Wang Z, Keller J, Banerjee P, Herman J, Cameron J, Yeo C, Halushka M, Eshleman J, Raben M, Klein A, Hruban R, Hidalgo M, Laheru D:DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009;27:1806-13. PMID 19273710
Ma WW, Jacene H, Song D, Vilardell F, Messersmith WA, Laheru D, Wahl R, Endres C, Jimeno A, Pomper MG, Hidalgo M. 18F]fluorodeoxyglucose positron emission tomography correlates with Akt pathway activity but is not predictive of clinical outcome during mTOR inhibitor therapy. J Clin Oncol 2009 Jun 1;27(16):2697-704. PMID: 19380450.
Benson AB 3rd, Abrams TA, Ben-Josef E, Bloomston PM, Botha JF, Clary BM, Covey A, Curley SA, D''Angelica MI, Davila R, Ensminger WD, Gibbs JF, Laheru D, Malafa MP, Marrero J, Meranze SG, Mulvihill SJ, Park JO, Posey JA, Sachdev J, Salem R, Sigurdson ER, Sofocleous C, Vauthey JN, Venook AP, Goff LW, Yen Y, Zhu AX. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw. 2009 Apr;7(4):350-91. PMID: 19406039.
Blackford A, Serrano OK, Wolfgang CL, Parmigiani G, Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Eshleman JR, Goggins M, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Cameron JL, Olino K, Schulick R, Winter J, Herman JM, Laheru D, Klein AP, Vogelstein B, Kinzler KW, Velculescu VE, Hruban RH: SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer: Clin Cancer Res. 2009 Jul 15;15(14):4674-9. Epub 2009 Jul 7. PMID: 19584151
Lutz E, Herman JM, Sugar E, Yeo C, Piantadosi S, Kobrin B, Biedrzycki B, Donehower R, Cameron J, Lillemoe K, Solt S, Onners B, Tartakovsky I, Choi M, Hruban R, Abrams R, Le D, Jaffee E, Laheru DA: A Safety and Efficacy Trial of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected with the GM-CSF Gene in Combination with Adjuvant Chemoradiotherapy for the Treatment of Adenocarcinoma of the Pancreas. Accepted to Annals of Surgery 2010
Weekes CD, Nallapareddy S, Rudek MA, Norris-Kirby A, Laheru D, Jimeno A, Donehower RC, Murphy KM, Hidalgo M, Baker SD, Messersmith WA: Thymidylate synthase (TYMS) enhancer region genotype-directed phase II trial of oral capecitabine for 2nd line treatment of advanced pancreatic cancer. Invest New Drugs. 2010 Mar 23. [Epub ahead of print] PMID: 20306339
Rasheed Z, Yang J, Wang Q, Kowalski J, Freed I, Murter C, Hong SM, JKoorstra JB, Rajeshkumar NV, He X, Goggins M, Iacobuzio-Donahue C, Berman D, Laheru D, Jimeno A, Hidalgo M, Maitra A, and Matsui W: Tumorigenic cells with mesenchymal features are prognostic in pancreatic adenocarcinoma. J Natl Cancer Inst. 2010 Mar 3;102(5):340-51. Epub 2010 Feb 17.PMID: 20164446
Hsu CC, Herman JM, Corsini MM, Winter JM, Callister MD, Haddock MG, Cameron JL, Pawlik TM, Schulick RD, Wolfgang CL, Laheru DA, Farnell MB, Swartz MJ, Gunderson LL, Miller RC: Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Ann Surg Oncol. 2010 Apr;17(4):981-90. Epub 2010 Jan 20.PMID: 20087786
Swartz MJ, Hsu CC, Pawlik TM, Winter J, Hruban RH, Guler M, Schulick RD, Cameron JL, Laheru DA, Wolfgang CL, Herman JM: Adjuvant chemoradiotherapy after pancreatic resection for invasive carcinoma associated with intraductal papillary mucinous neoplasm of the pancreas
. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):839-44. Epub 2009 Aug 3.PMID: 19647950
Voong, K.R.; Davison, J.; Pawlik, T.M.; Uy, M.O.; Hsu, C.C.; Winter, J.; Hruban, R.H.; Laheru, D.; Rudra, S.; Swartz, M.J.; Nathan, H.; Edil, B.H.; Schulick, R.; Cameron, J.L.; Wolfgang, C.L.; Herman, J.M. Resected pancreatic adenosquamous carcinoma: clinicopathologic review and evaluation of adjuvant chemotherapy and radiation in 38 patients. Hum Pathol. 2010 Jan;41(1):113-122.
Weekes, C.D.; Nallapareddy, S.; Rudek, M.A.; Norris-Kirby, A.; Laheru, D.; Jimeno, A.; Donehower, R.C.; Murphy, K.M.; Hidalgo, M.; Baker, S.D.; Messersmith, W.A. Thymidylate synthase (TYMS) enhancer region genotype-directed phase II trial of oral capecitabine for 2nd line treatment of advanced pancreatic cancer. Invest New Drugs. 2010 Mar 23.
Lutz, E.; Yeo, C.J.; Lillemoe, K.D.; Biedrzycki, B.; Kobrin, B.; Herman, J.; Sugar, E.; Piantadosi, S.; Cameron, J.L.; Solt, S.; Onners, B.; Tartakovsky, I.; Choi, M.; Sharma, R.; Illei, P.B.; Hruban, R.H.; Abrams, R.A.; Le, D.; Jaffee, E.; Laheru, D. A Lethally Irradiated Allogeneic Granulocyte-Macrophage Colony Stimulating Factor-Secreting Tumor Vaccine for Pancreatic Adenocarcinoma: A Phase II Trial of Safety, Efficacy, and Immune Activation. Ann Surg. 2011 Jan 6;Epub 1/11/11.
Villarroel, M.C.; Rajeshkumar, N.V.; Garrido-Laguna, I.; De Jesus-Acosta, A.; Jones, S.; Maitra, A.; Hruban, R.H.; Eshleman, J.R.; Klein, A.; Laheru, D.; Donehower, R.; Hidalgo, M. Personalizing Cancer Treatment in the Age of Global Genomic Analyses: PALB2 Gene Mutations and the Response to DNA Damaging Agents in Pancreatic Cancer. Mol Cancer Ther. 2011 Jan;10(1):3-8.