Gregory M. Springett, MD, PhD

Dr. Springett’s research has focused on validation and targeting of LPAAT-beta (lysophosphatidic acid acyltransferase; a phosphatidic acid generating enzyme that regulates cell growth and proliferation) in ovarian and pancreatic cancer. Accomplishments of Dr. Springett and colleagues in this area include: 1) demonstration that LPAAT-beta is over expressed in ovarian and endometrial cancers; 2) discovery that LPAAT-beta is a prognostic marker and that expression correlates with poor clinical outcome in ovarian cancer; 3) discovery that LPAAT-beta is expressed in pancreatic cancer; and 4) demonstration that small molecule inhibitors of LPAAT-beta have therapeutic potential in animal models of ovarian cancer. They are working to identify new LPAAT-beta inhibitor pharmacophores that are suitable for translation to phase I trials.

Their work also focuses on developing and implementing biomarker-driven therapeutics into patient-based therapeutic trials. They conducted a phase I dose-escalation study of MK-2461 (a selective inhibitor of c-Met, an oncogene that contributes to malignant transformation and tumor cell metastasis in patients with advanced cancer).  The biomarker-driven trial enrolled patients with evidence of c-Met activation in their tumor specimens to test safety, tolerability and preliminary efficacy.

• Ghansah T, Vohra N, Kinney K, Weber A, Kodumudi K, Springett G, Sarnaik AA, Pilon-Thomas S. Dendritic cell immunotherapy combined with gemcitabine chemotherapy enhances survival in a murine model of pancreatic carcinoma. Cancer Immunol Immunother. 2013 Apr. Pubmedid: 23604104.
• Chuong MD, Springett GM, Freilich JM, Park CK, Weber JM, Mellon EA, Hodul PJ, Malafa MP, Meredith KL, Hoffe SE, Shridhar R. Stereotactic Body Radiation Therapy for Locally Advanced and Borderline Resectable Pancreatic Cancer Is Effective and Well Tolerated. Int J Radiat Oncol Biol Phys. 2013 Apr. Pubmedid: 23562768.
• Kucera S, Centeno BA, Springett G, Malafa MP, Chen YA, Weber J, Klapman J. Cyst Fluid Carcinoembryonic Antigen Level Is not Predictive of Invasive Cancer in Patients with Intraductal Papillary Mucinous Neoplasm of the Pancreas. JOP. 2012 Jul;13(4):409-413. Pubmedid: 22797397.
• Jacobsen PB, Wells KJ, Meade CD, Quinn GP, Lee JH, Fulp WJ, Gray JE, Baz RC, Springett GM, Levine RM, Markham MJ, Schreiber FJ, Cartwright TH, Burke JM, Siegel RD, Malafa MP, Sullivan D. Effects of a brief multimedia psychoeducational intervention on the attitudes and interest of patients with cancer regarding clinical trial participation: a multicenter randomized controlled trial. J Clin Oncol. 2012 Jul;30(20):2516-2521. Pubmedid: 22614993.
• Mathew BM, Daas AY, Centeno BA, Hoffe S, Valone T, Patel M, Springett GM. Lessons learned from a complete remission of advanced metastatic pancreatic ductal adenocarcinoma. Clin Adv Hematol Oncol. 2012 May;10(5):340-343. Pubmedid: 22706548.
• Harris ES, Smith TL, Springett GM, Weyrich AS, Zimmerman GA. Leukocyte adhesion deficiency-I variant syndrome (LAD-Iv, LAD-III): molecular characterization of the defect in an index family. Am J Hematol. 2012 Mar;87(3):311-313. Pubmedid: 22139635. Pmcid: PMC3564639.
• Daud AI, Krishnamurthi SS, Saleh MN, Gitlitz BJ, Borad MJ, Gold PJ, Chiorean EG, Springett GM, Abbas R, Agarwal S, Bardy-Bouxin N, Hsyu PH, Leip E, Turnbull K, Zacharchuk C, Messersmith WA. Phase I Study of Bosutinib, a Src/Abl Tyrosine Kinase Inhibitor, Administered to Patients with Advanced Solid Tumors. Clin Cancer Res. 2012 Feb;18(4):1092-1100. Pubmedid: 22179664.
• Patel M, Hoffe S, Malafa M, Hodul P, Klapman J, Centeno B, Kim J, Helm J, Valone T, Springett G. Neoadjuvant GTX chemotherapy and IMRT-based chemoradiation for borderline resectable pancreatic cancer. J Surg Oncol. 2011 Aug;104(2):155-161. Pubmedid: 21520097. Pmcid: PMC3347705.
• Chuong MD, Hayman TJ, Patel MR, Russell MS, Malafa MP, Hodul PJ, Springett GM, Choi J, Shridhar R, Hoffe SE. Comparison of 1-, 2-, and 3-Dimensional Tumor Response Assessment After Neoadjuvant GTX-RT in Borderline-Resectable Pancreatic Cancer. Gastrointest Cancer Res. 2011 Jul;4(4):128-134. Pubmedid: 22368736. Pmcid: PMC3283109.
• Kindler HL, Ioka T, Richel DJ, Bennouna J, Létourneau R, Okusaka T, Funakoshi A, Furuse J, Park YS, Ohkawa S, Springett GM, Wasan HS, Trask PC, Bycott P, Ricart AD, Kim S, Van Cutsem E. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol. 2011 Mar;12(3):256-262. Pubmedid: 21306953.
• Gotoh L, Mitsuyasu H, Kobayashi Y, Oribe N, Takata A, Ninomiya H, Stanton VP, Springett GM, Kawasaki H, Kanba S. Association analysis of adenosine A1 receptor gene (ADORA1) polymorphisms with schizophrenia in a Japanese population. Psychiatr Genet. 2009 Dec;19(6):328-335. Pubmedid: 19820430.
• Wasan HS, Springett GM, Chodkiewicz C, Wong R, Maurel J, Barone C, Rosbrook B, Ricart AD, Kim S, Spano JP. CA 19-9 as a biomarker in advanced pancreatic cancer patients randomised to gemcitabine plus axitinib or gemcitabine alone. Br J Cancer. 2009 Oct;101(7):1162-1167. Pubmedid: 19724276. Pmcid: PMC2768104.
• Kazi A, Lawrence H, Guida WC, McLaughlin ML, Springett GM, Berndt N, Yip RM, Sebti SM. Discovery of a novel proteasome inhibitor selective for cancer cells over non-transformed cells. Cell Cycle. 2009 Jun;8(12):1940-1951. Pubmedid: 19471122. Pmcid: PMC2892826.
• Springett GM, Hoffe SE. Borderline resectable pancreatic cancer: on the edge of survival. Cancer Control. 2008 Oct;15(4):295-307. Pubmedid: 18813197.
• Mitsuyasu H, Kawasaki H, Ninomiya H, Kinukawa N, Yamanaka T, Tahira T, Stanton VP J, Springett G, Hayashi K, Tashiro N, Kanba S. Genetic structure of the dopamine receptor D4 gene (DRD4) and lack of association with schizophrenia in Japanese patients. J Psychiatr Res. 2007 Nov;41(9):763-775. Pubmedid: 16887146.
• Homsi J, Simon G, Garrett C, Springett G, DeConti R, Chiappori A, Munster PN, Burton M, Stromatt S, Allievi C, Angiuli P, Eisenfeld A, Sullivan D, Daud A. Phase I Trial of Poly-L-Glutamate Camptothecin (CT-2106) Administered Weekly in Patients with Advanced Solid Malignancies. Clin Cancer Res. 2007 Oct;13(19):5855-5861. Pubmedid: 17908979.
• Fracasso PM, Burris H, Arquette MA, Govindan R, Gao F, Wright LP, Goodner SA, Greco FA, Jones SF, Willcut N, Chodkiewicz C, Pathak A, Springett GM, Simon GR, Sullivan DM, Marcelpoil R, Mayfield SD, Mauro D, Garrett CR. A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing. Clin Cancer Res. 2007 Feb;13(3):986-993. Pubmedid: 17289894.
• Yendluri V, Centeno B, Springett G. Pancreatic cancer presenting as a Sister Mary Joseph's nodule: case report and update of the literature. Pancreas. 2007 Jan;34(1):161-164. Pubmedid: 17198200.
• Springett GM, Bonham L, Hummer A, Linkov I, Misra D, Ma C, Pezzoni G, Di Giovine S, Singer J, Kawasaki H, Spriggs D, Soslow R, Dupont J. Lysophosphatidic acid acyltransferase-beta is a prognostic marker and therapeutic target in gynecologic malignancies. Cancer Res. 2005 Oct;65(20):9415-9425. Pubmedid: 16230405.
• Springett GM, Kawasaki H, Spriggs DR. Non-kinase second-messenger signaling: new pathways with new promise. Bioessays. 2004 Jul;26(7):730-738. Pubmedid: 15221855.
• Alberta J, Springett G, Rayburn H, Natoli T, Kriedberg J, Housman D. Role of the WT1 tumor suppressor in murine hematopoiesis. Blood. 2003;101(7):2570-2574. Pubmedid: 12468434.
• Kawasaki H, Springett GM, Toki S, Canales JJ, Harlan P, Blumenstiel JP, Chen EJ, Bany IA, Mochizuki N, Ashbacher A, Matsuda M, Housman DE, Graybiel AM. A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc Natl Acad Sci U S A. 1998 Oct;95(22):13278-13283. Pubmedid: 9789079. Pmcid: PMC23782.
• Zhang G, Feygelman V, Stevens C, Li W, Leuthold S, Springett G, Hoffe S. Re-planning for compensator-based IMRT with original compensators. Med Dosim. 2011 Winter;36(1):102-108. Pubmedid: 20207532.