Targeting SRC family kinases in mesothelioma: Time to upgrade

Paola Indovina, Iris Maria Forte, Francesca Pentimalli, Antonio Giordano

Research output: Contribution to journalReview articlepeer-review

Abstract

Malignant mesothelioma (MM) is a deadly tumor mainly caused by exposure to asbestos. Unfortunately, no current treatment is able to change significantly the natural history of the disease, which has a poor prognosis in the majority of patients. The non-receptor tyrosine kinase SRC and other SRC family kinase (SFK) members are frequently hyperactivated in many cancer types, including MM. Several works have indeed suggested that SFKs underlie MM cell proliferation, survival, motility, and invasion, overall affecting multiple oncogenic pathways. Consistently, SFK inhibitors effectively counteracted MM cancerous features at the preclinical level. Dasatinib, a multi-kinase inhibitor targeting SFKs, was also assessed in clinical trials either as second-line treatment for patients with unresectable MM or, more recently, as a neoadjuvant agent in patients with resectable MM. Here, we provide an overview of the molecular mechanisms implicating SFKs in MM progression and discuss possible strategies for a more successful clinical application of SFK inhibitors. Our aim is to stimulate discussion and further consideration of these agents in better designed preclinical and clinical studies to make the most of another class of powerful antitumoral drugs, which too often are lost in translation when applied to MM.

Original languageEnglish
Article number1866
Pages (from-to)1-21
Number of pages21
JournalCancers
Volume12
Issue number7
DOIs
Publication statusPublished - Jul 2020

Keywords

  • AKT
  • Dasatinib
  • Drug combination
  • Invasion
  • Malignant mesothelioma
  • P27
  • Predictive signature
  • Receptor tyrosine kinases
  • SRC family kinases
  • Treatment resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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