title: Targeting mTOR in Pancreatic Ductal Adenocarcinoma.
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.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
authors.forename: Sentia
authors.initials: S
authors.lastname: Iriana
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
authors.forename: Shahzad
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
authors.forename: Alagappan Anand
authors.initials: AA
authors.lastname: Annamalai
authors.affiliation: Department of Radiation Oncology, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Tuli
authors.affiliation: Department of Medicine, Division of Medical Oncology, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
authors.forename: Andrew Eugene
authors.initials: AE
authors.lastname: Hendifar
keywords: KRAS; clinical trials; mTOR; pancreatic ductal adenocarcinoma; preclinical