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Review
. 2016 Apr 25:6:99.
doi: 10.3389/fonc.2016.00099. eCollection 2016.

Targeting mTOR in Pancreatic Ductal Adenocarcinoma

Sentia Iriana  1 , Shahzad Ahmed  1 , Jun Gong  2 , Alagappan Anand Annamalai  3 , Richard Tuli  4 , Andrew Eugene Hendifar  5
Affiliations
Review

Targeting mTOR in Pancreatic Ductal Adenocarcinoma

Sentia Iriana et al. Front Oncol. .

Abstract

Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited; however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data have shown that inhibition of mammalian target of rapamycin (mTOR) in specific KRAS-dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro and in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS-dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future.

Keywords: KRAS; clinical trials; mTOR; pancreatic ductal adenocarcinoma; preclinical.

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References

    1. Howlader N, Noone A, Krapcho M, Garshell J, Miller D, Altekruse S, et al. SEER Cancer Statistics Review, 1975-2011. (2013). Available from: http://seer.cancer.gov/csr/1975_2011/
    1. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med (2014) 371:1039–49.10.1056/NEJMra1404198 - DOI - PubMed
    1. Wei F, Zhang Y, Geng L, Zhang P, Wang G, Liu Y. mTOR inhibition induces EGFR feedback activation in association with its resistance to human pancreatic cancer. Int J Mol Sci (2015) 16:3267–82.10.3390/ijms16023267 - DOI - PMC - PubMed
    1. Chari ST, Leibson CL, Rabe KG, Ransom J, de Andrade M, Petersen GM. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology (2005) 129:504–11.10.1016/j.gastro.2005.05.007 - DOI - PMC - PubMed
    1. Konstantinidis IT, Warshaw AL, Allen JN, Blaszkowsky LS, Castillo CF, Deshpande V, et al. Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a “true” R0 resection? Ann Surg (2013) 257:731–6.10.1097/SLA.0b013e318263da2f - DOI - PubMed