Targeting leukemia inhibitory factor in pancreatic adenocarcinoma

Introduction: The Leukemia Inhibitory Factor (LIF) is a member of the interleukin-6 (IL-6) cytokine family. Known to induce differentiation of myeloid leukemia cells, evidence has accumulated supporting its role in cancer evolution through regulating cell differentiation, renewal, and survival. LIF has recently emerged as a biomarker and therapeutic target for pancreatic ductal adenocarcinoma (PDAC). The first in-human clinical trial has shown promising safety profile and has suggested a potential role for LIF inhibitor in combination regimen. Areas covered: Herein, we summarize, discuss, and give an expert opinion on the role of LIF in PDAC promotion, and its potential role as a biomarker and target of anti-cancer therapy. We conducted an exhaustive PubMed search for English-language articles published from 1 January 1970, to 1 August 2022. Expert opinion: PDAC carries a devastating prognosis for patients, highlighting the need for advancing drug development. The results of the phase 1 trial with MSC-1 demonstrated tolerability and safety but modest efficacy. Future research should focus on investigating LIF targets in combination with current standard-of-care chemotherapy, and immunotherapy can be a promising approach. Further, larger multicenter clinical trials are needed to define the use of LIF as a new biomarker in PDAC patients.