Drug Resistance in Non-Small Cell Lung Cancer: A Potential for NOTCH Targeting?

Venus Sosa Iglesias, Lorena Giuranno, Ludwig J. Dubois, Jan Theys, Marc Vooijs*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

74 Citations (Web of Science)

Abstract

Drug resistance is a major cause for therapeutic failure in non-small cell lung cancer (NSCLC) leading to tumor recurrence and disease progression. Cell intrinsic mechanisms of resistance include changes in the expression of drug transporters, activation of pro-survival, and anti-apoptotic pathways, as well as non-intrinsic influences of the tumor microenvironment. It has become evident that tumors are composed of a heterogeneous population of cells with different genetic, epigenetic, and phenotypic characteristics that result in diverse responses to therapy, and underlies the emergence of resistant clones. This tumor heterogeneity is driven by subpopulations of tumor cells termed cancer stem cells (CSCs) that have tumor-initiating capabilities, are highly self-renewing, and retain the ability for multi-lineage differentiation. CSCs have been identified in NSCLC and have been associated with chemo-and radiotherapy resistance. Stem cell pathways are frequently deregulated in cancer and are implicated in recurrence after treatment. Here, we focus on the NOTCH signaling pathway, which has a role in stem cell maintenance in non-squamous non-small lung cancer, and we critically assess the potential for targeting the NOTCH pathway to overcome resistance to chemotherapeutic and targeted agents using both preclinical and clinical evidence.

Original languageEnglish
Article number267
Number of pages23
JournalFrontiers in Oncology
Volume8
DOIs
Publication statusPublished - 24 Jul 2018

Keywords

  • non-small cell lung cancer
  • treatment resistance
  • NOTCH/gamma-secretase inhibitor
  • chemotherapy
  • targeted therapy
  • GAMMA-SECRETASE INHIBITOR
  • ADVANCED SOLID TUMORS
  • NF-KAPPA-B
  • EPITHELIAL-MESENCHYMAL TRANSITION
  • ACUTE LYMPHOBLASTIC-LEUKEMIA
  • CISPLATIN-BASED CHEMOTHERAPY
  • STEM-LIKE CELLS
  • PHASE-I
  • SIGNALING PATHWAY
  • NEUROENDOCRINE CARCINOMA

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