Targeting mTOR in Pancreatic Ductal Adenocarcinoma

Sentia Iriana; Shahzad Ahmed; Jun Gong; Alagappan Anand Annamalai; Richard Tuli; Andrew Eugene Hendifar

doi:10.3389/fonc.2016.00099

Targeting mTOR in Pancreatic Ductal Adenocarcinoma

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

Authors

Sentia Iriana¹, Shahzad Ahmed¹, Jun Gong², Alagappan Anand Annamalai³, Richard Tuli⁴, Andrew Eugene Hendifar⁵

Affiliations

¹ Department of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
² Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
³ Department of Surgery, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
⁴ Department of Radiation Oncology, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
⁵ Department of Medicine, Division of Medical Oncology, Cedars-Sinai Medical Center , Los Angeles, CA , USA.

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.

Publication types

Review