Pancreatic cancer is the fourth most common cause of cancer death (~30,000 deaths annually) in men and women in the United States, with five-year survival for all stages of disease less than 5 percent. Despite several phase II trials of chemo-radiotherapy regimens, no clinically meaningful gains have been made in the treatment of pancreatic cancer. There is an urgent need for more effective therapy for patients with advanced disease. Potential approaches might include genetic-based therapies that attempt to eradicate cancer cells by manipulating their intracellular genetic material with strategies ranging from restoring the function of mutated or missing tumor suppressor genes to inhibiting the function of activated oncogenes.
One such strategy is to utilize the inhibitor of apoptosis (IAP), survivin, as a therapeutic target as it is overexpressed in cancer but undetectable in normal differentiated adult tissues. Survivin expression in cancer appears to be associated with unfavorable clinicopathological parameters, such as poor prognosis with progressive disease and shorter patient survival rates. Survivin is also expressed in the majority of pancreatic adenocarcinomas and correlates with cellular proliferation and apoptosis. My laboratory seeks to further elucidate the cellular pathways and molecular interactions taking place between survivin and members of the apoptosome and to evaluate whether pancreatic cancer can be treated by targeting survivin both in vitro and in vivo.
- Khan S, Aspe JR, Asumen MG, Almaguel F, Odumosu O, Acevedo-Martinez S, De Leon M, Langridge W, Wall NR. Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. British Journal of Cancer 100(7):1073-1086, 2009.
- Galloway NR, Aspe JR, Sellers C, Wall NR. Enhanced antitumor effect of combined gemcitabine and proton radiation in the treatment of pancreatic cancer. Pancreas 38(7) 782-790, 2009.
- Aspe JR and Wall NR. Survivin-T34A: molecular mechanism and therapeutic potential. OncoTargets and Therapy, 3:247-254, 2010.
- Khan S, Jutzy JMS, Aspe JR, McGregor D, Neidigh JW, Wall NR. Survivin is released from cancer cells via exosomes. Apoptosis, 16(1): 1-12, 2011.
- Khan S, Jutzy JMS, Valenzuela MMA, Turay D, Aspe JR, Ashok A, Mirshahidi S, Mercola D, Lilly MB, Wall NR. Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer. PLoS One, 7(10): 1-10, 2012.
- Jutzy JMS, Khan S, Valenzuela MMA, Milford TM, Payne KJ, Wall NR. Tumor-released survivin inhibits T cell proliferation and alters CD4+ T cell cytokine profiles to induce a pro-tumor environment. Cancer Microenvironment, 6(1): 57-68, 2013.
- de Necochea-Campion R, Chen CS, Mirshahidi S, Howard FD, Wall NR. Clinico-Pathologic Relevance of Survivin Splice Variant Expression in Cancer. Cancer Letters, 339(2): 167-174, 2013.
- Aspe JR, Diaz Osterman CJ, Jutzy JMS, Deshields S, Whang S, Wall NR. Enhancement of Gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant. J Extracellular Vesicles, 3: 1-9, 2014.
- Khan S, Ferguson H, Turay D, Perez M, Mirshahidi S, Yuan Y, Wall NR. Early diagnostic value of Survivin and its alternative splice variants in breast cancer. BMC Cancer, 14(1):176, 2014.
- Galloway NR, Diaz Osterman CJ, Reiber K, Jutzy JMS, Li F, Sui G, Soto U, Wall NR. Ying Yang 1 regulates the transcriptional repression of Survivin. Biochemical and Biophysical Research Communications, 445(1): 208-213, 2014.
- Valenzuela MMA, Neidigh JW, Wall NR. Antimetabolite treatment for Pancreatic Cancer. Chemotherapy, 3(3): 1-7, 2014.
- Valenzuela MMA, Castro IV, Gonda A, Osterman CD, Jutzy JMS, Aspe JR, Khan S, Neidigh JW, Wall NR. Cell death in response to antimetabolites directed at ribonucleotide reductase and thymidylate synthase. OncoTargets and Therapy, 8: 495-507, 2015.
- Valenzuela MMA, Ferguson Bennit HR, Gonda A, Diaz-Osterman CJ, Hibma A, Khan S, Wall NR. Exosomes secreted from human cancer cell lines contain inhibitor of apoptosis (IAP). Cancer Microenvironment, 8(2): 65-73, 2015.
- Diaz Osterman CJ, Lynch JC, Leaf P, Gonda A, Fergusen Bennit HR, Griffiths D, Wall NR. Curcumin modulates pancreatic adenocarcinoma cell-derived exosomal function. Accepted for Publication, PLoS One, 10(7): e0132845, 2015.
- Díaz Osterman CJ, Gonda A, Stiff TR, Sigaran U, Asuncion Valenzuela MM, Ferguson Bennit H, Moyron RB, Khan S, Wall NR. Curcumin Induces Pancreatic Adenocarcinoma Cell Death via Reduction of the Inhibitors of Apoptosis. Accepted for Publication, Pancreas, 2015.
- Turay D, Khan S, Osterman CD, Curtis MP, Khaira B, Neidigh JW, Mirshahidi S, Casiano CA, Wall NR. Proteomic profiling of serum-derived exosomes from ethnically diverse prostate cancer patients. Accepted for Publication, Cancer Investigation, 2015.