RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients

Oncotarget

Volumn 6, Issue 27, 2015, Pages 24560-24570

  Golan, Talia ^a   Khvalevsky, Elina Zorde ^b   Hubert, Ayala ^c   Gabai, Rachel Malka ^b   Hen, Naama ^b   Segal, Amiel ^d   Domb, Abraham ^e   Harari, Gil ^f   David, Eliel Ben ^c   Raskin, Stephen ^a   Goldes, Yuri ^a   Goldin, Eran ^d   Eliakim, Rami ^a   Lahav, Maor ^a   Kopleman, Yael ^c   Dancour, Alain ^d   Shemi, Amotz ^b   Galun, Eithan ^c  

^a TEL AVIV UNIVERSITY   (Israel)

^b Silenseed Ltd   (Israel)

^c HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^d SHAARE ZEDEK MEDICAL CENTER   (Israel)

^e HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^f Medis El Ltd   (Israel)

Author keywords

KRAS; Overall survival; Pancreatic cancer; Polymer implant; SiRNA

Indexed keywords

ERLOTINIB; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; IRINOTECAN; K RAS PROTEIN; OXALIPLATIN; SMALL INTERFERING RNA; ANTINEOPLASTIC AGENT; CAMPTOTHECIN; DEOXYCYTIDINE; DRUG IMPLANT; KRAS PROTEIN, HUMAN; PLATINUM COMPLEX; PROTEIN P21; TUMOR ANTIGEN;

ABDOMINAL PAIN; ADULT; ADVANCED CANCER; ALOPECIA; ANEMIA; ARTICLE; BACKACHE; BIODEGRADABLE IMPLANT; BIOPSY NEEDLE; CANCER GROWTH; CANCER SURVIVAL; CHOLANGITIS; CLINICAL ARTICLE; COLON OBSTRUCTION; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ENDOSCOPY; FATIGUE; FEMALE; FEVER; FLU LIKE SYNDROME; HUMAN; INFUSION RELATED REACTION; KIDNEY FAILURE; LOCALLY ADVANCED PANCREATIC CANCER; MALE; MULTICENTER STUDY; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PANCREAS CANCER; PANCREATITIS; PANCYTOPENIA; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PROGRESSION FREE SURVIVAL; RASH; RECOMMENDED DRUG DOSE; RNA INTERFERENCE; SINGLE DRUG DOSE; THROMBOCYTE COUNT; VOMITING; AGED; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; BLOOD; CARCINOMA, PANCREATIC DUCTAL; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DRUG IMPLANT; GENETICS; MIDDLE AGED; MOLECULARLY TARGETED THERAPY; MULTIMODALITY CANCER THERAPY; PANCREATIC NEOPLASMS; PROCEDURES; RNAI THERAPEUTICS; VERY ELDERLY;

ABSORBABLE IMPLANTS; AGED; AGED, 80 AND OVER; ANTIGENS, NEOPLASM; ANTINEOPLASTIC AGENTS; CAMPTOTHECIN; CARCINOMA, PANCREATIC DUCTAL; COMBINED MODALITY THERAPY; DEOXYCYTIDINE; DISEASE-FREE SURVIVAL; DRUG IMPLANTS; FEMALE; FLUOROURACIL; HUMANS; LEUCOVORIN; MALE; MIDDLE AGED; MOLECULAR TARGETED THERAPY; ORGANOPLATINUM COMPOUNDS; PANCREATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS P21(RAS); RNA, SMALL INTERFERING; RNAI THERAPEUTICS;

EID: 84941262148     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.4183     Document Type: Article

References (21)

1. Delpu Y, Hanoun N, Lulka H, et al. Genetic and epigenetic alterations in pancreatic carcinogenesis. Curr Genomics 2011;12:15-24.
2. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-703.
3. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-25.
4. Iacobuzio-Donahue CA, Fu B, Yachida S, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009;27:1806-13.
5. Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol 2008;19:1592-9.
6. Loehrer PJ, Sr., Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer:an Eastern Cooperative Oncology Group trial. J Clin Oncol 2011;29:4105-12.
7. Herman JM, Wild AT, Wang H, et al. Randomized Phase III Multi-Institutional Study of TNFerade Biologic With Fluorouracil and Radiotherapy for Locally Advanced Pancreatic Cancer:Final Results. J Clin Oncol 2013;31:886-94.
8. Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant Modified (m) FOLFIRINOX for Locally Advanced Unresectable (LAPC) and Borderline Resectable (BRPC) Adenocarcinoma of the Pancreas. Ann Surg Oncol 2014.
9. Belda-Iniesta C, Ibanez de Caceres I, Barriuso J, et al. Molecular biology of pancreatic cancer. Clin Transl Oncol 2008;10:530-7.
10. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008;321:1801-6.
11. Feldmann G, Beaty R, Hruban RH, et al. Molecular genetics of pancreatic intraepithelial neoplasia. J Hepatobiliary Pancreat Surg 2007;14:224-32.
12. Villanueva A, Reyes G, Cuatrecasas M, et al. Diagnostic utility of K-ras mutations in fine-needle aspirates of pancreatic masses. Gastroenterology 1996;110:1587-94.
13. Sun C, Yamato T, Furukawa T, et al. Characterization of the mutations of the K-ras, p53, p16, and SMAD4 genes in 15 human pancreatic cancer cell lines. Oncol Rep 2001;8:89-92.
14. Singh A, Greninger P, Rhodes D, et al. A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival. Cancer Cell 2009;15:489-500.
15. John J, Sohmen R, Feuerstein J, et al. Kinetics of interaction of nucleotides with nucleotide-free H-ras p21. Biochemistry 1990;29:6058-65.
16. Wu SY, Lopez-Berestein G, Calin GA, et al. RNAi therapies:drugging the undruggable. Sci Transl Med 2014;6:240ps7.
17. Fleming JB, Shen GL, Holloway SE, et al. Molecular consequences of silencing mutant K-ras in pancreatic cancer cells:justification for K-ras-directed therapy. Mol Cancer Res 2005;3:413-23.
18. Rejiba S, Wack S, Aprahamian M, et al. K-ras oncogene silencing strategy reduces tumor growth and enhances gemcitabine chemotherapy efficacy for pancreatic cancer treatment. Cancer Sci 2007;98:1128-36.
19. Zorde Khvalevsky E, Gabai R, Rachmut IH, et al. Mutant KRAS is a druggable target for pancreatic cancer. Proc Natl Acad Sci U S A 2013;110:20723-8.
20. Kim SH, Jeong JH, Lee SH, et al. Local and systemic delivery of VEGF siRNA using polyelectrolyte complex micelles for effective treatment of cancer. J Control Release 2008;129:107-16.
21. Ziske C, Schlie C, Gorschluter M, et al. Prognostic value of CA 19-9 levels in patients with inoperable adenocarcinoma of the pancreas treated with gemcitabine. Br J Cancer 2003;89:1413-7.