Targeting pi3k pathway in pancreatic ductal adenocarcinoma: Rationale and progress

Siddharth Mehra, Nilesh Deshpande, Nagaraj Nagathihalli

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest solid tumors that re-main treatment‐refractory and show a dismal prognosis. More than 90% of PDAC tumors harbor mutations in the K‐Ras that exert a strong pro‐tumorigenic effect by activating several downstream effector pathways, including phosphatidylinositol‐3‐kinase (PI3K)‐Akt. The role of frequently activated PI3K/Akt pathway in promoting PDAC aggressiveness is well established. Therapeutic approaches targeting PI3K and downstream signaling components in different cellular compartments, including tumor, stromal and immune cells, have directly impacted the tumor burden in this cancer type. Our previous work has demonstrated that targeting the PI3K/Akt/mTOR pathway reduced tumor growth and improved survival in the genetic mouse model of PDAC. Here, we discuss the significance of targeting PI3K signaling and the biological impact of PI3K inhibition in modulating the tumor–stromal immune cross-talk within the microenvironment of pancreatic cancer. Furthermore, this review updates on the current challenges involving the therapeutic implications of targeting this pathway in PDAC.

Original languageEnglish (US)
Article number4434
JournalCancers
Volume13
Issue number17
DOIs
StatePublished - Sep 2021

Keywords

  • Immune microenvironment
  • PI3K/Akt pathway
  • Pancreatic cancer
  • RAS
  • Tumor‐stromal crosstalk
  • Urolithin A

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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