Safety and Biologic Response of Pre-operative Autophagy Inhibition in Combination with Gemcitabine in Patients with Pancreatic Adenocarcinoma

Annals of Surgical Oncology

Volumn 22, Issue 13, 2015, Pages 4402-4410

  Boone, Brian A ^a   Bahary, Nathan ^b   Zureikat, Amer H ^a   Moser, A James ^e   Normolle, Daniel P ^c   Wu, Wen Chi ^c   Singhi, Aatur D ^b   Bao, Phillip ^a   Bartlett, David L ^a   Liotta, Lance A ^d   Espina, Virginia ^d   Loughran, Patricia ^a   Lotze, Michael T ^a   Zeh, Herbert J ^a  

^a UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PITTSBURGH GRADUATE SCHOOL OF PUBLIC HEALTH   (United States)

^d GEORGE MASON UNIVERSITY   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CA 19-9 ANTIGEN; GEMCITABINE; HYDROXYCHLOROQUINE; PROTEIN P53; TUMOR MARKER; ANTINEOPLASTIC ANTIMETABOLITE; ANTIRHEUMATIC AGENT; BIOLOGICAL MARKER; DEOXYCYTIDINE;

ADULT; ARTICLE; AUTOPHAGY; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER SURGERY; CANCER SURVIVAL; CLINICAL ARTICLE; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DOSIMETRY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LIVER METASTASIS; MALE; MESENTERIC VEIN THROMBOSIS; MULTIPLE ORGAN FAILURE; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PANCREAS ADENOCARCINOMA; PANCREAS SURGERY; PANCREATIC LEAK; PANCREATICODUODENECTOMY; PERIPHERAL BLOOD MONONUCLEAR CELL; PROSPECTIVE STUDY; STEREOTACTIC BODY RADIATION THERAPY; STORER DOSE ESCALATION DESIGN; SUPERIOR MESENTERIC VEIN; SURGICAL MORTALITY; TREATMENT RESPONSE; VEIN ANASTOMOSIS; VEIN SURGERY; VENOUS RESECTION; ADENOCARCINOMA; AGED; ANALOGS AND DERIVATIVES; CANCER STAGING; COMBINATION DRUG THERAPY; DRUG EFFECTS; ENZYME IMMUNOASSAY; FOLLOW UP; METABOLISM; MIDDLE AGED; MORTALITY; MULTICENTER STUDY; PANCREATIC NEOPLASMS; PATHOLOGY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PROGNOSIS; SAFETY; SURVIVAL RATE; VERY ELDERLY;

ADENOCARCINOMA; ADULT; AGED; AGED, 80 AND OVER; ANTIMETABOLITES, ANTINEOPLASTIC; ANTIRHEUMATIC AGENTS; AUTOPHAGY; BIOMARKERS; CA-19-9 ANTIGEN; DEOXYCYTIDINE; DRUG THERAPY, COMBINATION; FEMALE; FOLLOW-UP STUDIES; HUMANS; HYDROXYCHLOROQUINE; IMMUNOENZYME TECHNIQUES; MALE; MIDDLE AGED; NEOPLASM STAGING; PANCREATIC NEOPLASMS; PROGNOSIS; PROSPECTIVE STUDIES; SAFETY; SURVIVAL RATE;

EID: 84947128722     PISSN: 10689265     EISSN: 15344681     Source Type: Journal    
DOI: 10.1245/s10434-015-4566-4     Document Type: Article

References (41)

1. Mathew R, White E. Autophagy, stress, and cancer metabolism: what doesn’t kill you makes you stronger. Cold Spring Harb Symp Quant Biol. 2011;76:389–96.
2. Maycotte P, Thorburn A. Autophagy and cancer therapy. Cancer Biol Ther. 2011;11:127–37.
3. Buchser WJ, Laskow TC, Pavlik PJ, Lin HM, Lotze MT. Cell-mediated autophagy promotes cancer cell survival. Cancer Res. 2012;72:2970–9.
4. Kang R, Tang D. Autophagy in pancreatic cancer pathogenesis and treatment. Am J Cancer Res. 2012;2:383–96.
5. Kang R, Tang D, Lotze MT, Zeh HJ 3rd. AGER/RAGE-mediated autophagy promotes pancreatic tumorigenesis and bioenergetics through the IL6-pSTAT3 pathway. Autophagy. 2012;8:989–91.
6. Kang R, Loux T, Tang D, Schapiro NE, Vernon P, Livesey KM, et al. The expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia. Proc Natl Acad Sci USA. 2012;109:7031–6.
7. Kang R, Tang D, Schapiro NE, Livesey KM, Farkas A, Loughran P, et al. The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ. 2010;17:666–76.
8. Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 2011;25:717–29.
9. Wang Y, Wang XD, Lapi E, Sullivan A, Jia W, He YW, et al. Autophagic activity dictates the cellular response to oncogenic RAS. Proc Natl Acad Sci USA. 2012;109:13325–30.
10. Kang R, Tang D, Lotze MT, Zeh HJ 3rd. RAGE regulates autophagy and apoptosis following oxidative injury. Autophagy. 2011;7:442–4.
11. Kang R, Tang D, Loze MT, Zeh HJ. Apoptosis to autophagy switch triggered by the MHC class III–encoded receptor for advanced glycation endproducts (RAGE). Autophagy. 2011;7:91–3.
12. Fujii S, Mitsunaga S, Yamazaki M, Hasebe T, Ishii G, Kojima M, et al. Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome. Cancer Sci. 2008;99:1813–9.
13. Mirzoeva OK, Hann B, Hom YK, Debnath J, Aftab D, Shokat K, et al. Autophagy suppression promotes apoptotic cell death in response to inhibition of the PI3K-mTOR pathway in pancreatic adenocarcinoma. J Mol Med (Berl). 2011;89:877–89.
14. Livesey KM, Tang D, Zeh HJ, Lotze MT. Autophagy inhibition in combination cancer treatment. Curr Opin Investig Drugs. 2009;10:1269–79.
15. Munster T, Gibbs JP, Shen D, Baethge BA, Botstein GR, Caldwell J, et al. Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis. Arthritis Rheum. 2002;46:1460–9.
16. Momose Y, Arai S, Eto H, Kishimoto M, Okada M. Experience with the use of hydroxychloroquine for the treatment of lupus erythematosus. J Dermatol. 2013;40:94–7.
17. Amaravadi RK, Lippincott-Schwartz J, Yin XM, Weiss WA, Takebe N, Timmer W, et al. Principles and current strategies for targeting autophagy for cancer treatment. Clin Cancer Res. 2011;17:654–66.
18. Bao P, Potter D, Eisenberg DP, Lenzner D, Zeh HJ, Lee Iii KK, et al. Validation of a prediction rule to maximize curative (R0) resection of early-stage pancreatic adenocarcinoma. HPB (Oxford). 2009;11:606–11.
19. Storer BE. Design and analysis of phase I clinical trials. Biometrics. 1989;45:925–37.
20. Bao P, Potter D, Eisenber DP, Lenzner D, Zeh HJ, Lee KK, et al. Validation of a prediction rule to maximize curative (R0) resection of early-stage pancreatic adenocarcinoma. HPB (Oxford). 2009;11:606–11.
21. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.
22. Evans DB, Rich TA, Byrd DR, Cleary KR, Connelly JH, Levin B, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127:1335–9.
23. Oshima M, Okano K, Muraki S, Haba R, Maeba T, Suzuki Y, et al. Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer. Ann Surg. 2013;258:336–46.
24. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.
25. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.
26. Hammad N, Heilbrun LK, Philip PA, Shields AF, Zalupski MM, Venkatramanamoorthy R, et al. CA19-9 as a predictor of tumor response and survival in patients with advanced pancreatic cancer treated with gemcitabine based chemotherapy. Asia Pac J Clin Oncol. 2010;6:98–105.
27. Haeno H, Gonen M, Davis MB, Herman JM, Iacobuzio-Donahue CA, Michor F. Computational modeling of pancreatic cancer reveals kinetics of metastasis suggesting optimum treatment strategies. Cell. 2012;148:362–75.
28. Bauer TM, El-Rayes BF, Li X, Hammad N, Philip PA, Shields AF, et al. Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials. Cancer. 2013;119:285–92.
29. 18FDG-PET response on outcomes in patients with locally advanced pancreatic carcinoma treated with definitive concurrent chemoradiotherapy. BMC Gastroenterol. 2011;11:123.
30. Gnerlich JL, Luka SR, Deshpande AD, Dubray BJ, Weir JS, Carpenter DH, et al. Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch Surg. 2012;147:753–60.
31. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012;8:445–544.
32. Wolpin BM, Rubinson DA, Wang X, Chan JA, Cleary JM, Enzinger PC, et al. Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist. 2014;19:637–8.
33. Rosenfeldt MT, O’Prey J, Morton JP, Nixon C, MacKay G, Mrowinska A, et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature. 2013;504(7479):296–300.
34. Iacobuzio-Donahue CA, Herman JM. Autophagy, p53, and pancreatic cancer. N Engl J Med. 2014;370:1352–3.
35. Starobinets H, Debnath J. Cancer: a suppression switch. Nature. 2013;504(7479):225–6.
36. Hashimoto D, Blauer M, Hirota M, Ikonen NH, Sand J, Laukkarinen J. Autophagy is needed for the growth of pancreatic adenocarcinoma and has a cytoprotective effect against anticancer drugs. Eur J Cancer. 2014;50:1382–90.
37. Donohue E, Thomas A, Maurer N, Manisali I, Zeisser-Labouebe M, Zisman N, et al. The autophagy inhibitor verteporfin moderately enhances the antitumor activity of gemcitabine in a pancreatic ductal adenocarcinoma model. J Cancer. 2013;4:585–96.
38. Papademetrio DL, Cavaliere V, Simunovich T, Costantino S, Campos MD, Lombardo T, et al. Interplay between autophagy and apoptosis in pancreatic tumors in response to gemcitabine. Target Oncol. 2014;9:123–34.
39. Yang A, Rajeshkumar NV, Wang X, Yabuuchi S, Alexander BM, Chu GC, et al. Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations. Cancer Discov. 2014;4:905–13.
40. Yang S, Kimmelman AC. A critical role for autophagy in pancreatic cancer. Autophagy. 2011;7:912–3.
41. Kim H, Saka B, Knight S, Borges M, Childs E, Klein A, et al. Having pancreatic cancer with tumoral loss of ATM and normal TP53 protein expression is associated with a poorer prognosis. Clin Cancer Res. 2014;20:1865–72.