Immunotherapy in Non-Small-Cell Lung Cancer Patients with Driver Alterations: A New Strategy?

Cells. 2022 Oct 18;11(20):3280. doi: 10.3390/cells11203280.

Abstract

For many years, researchers have been trying to develop the most effective ways to fight lung cancer, which is the cause of the largest number of cancer-related deaths among men and women worldwide. The most advanced treatments for nearly all non-small-cell lung cancer (NSCLC) types include immunotherapy with immune checkpoint inhibitors (ICIs), mainly anti-programmed death 1/anti-programmed death ligand 1 monoclonal antibodies (anti-PD-1/PD-L1 mAbs) in monotherapy or in combination with other strategies. Despite significant advances, long survival is not achievable in most cases, so new solutions are constantly being sought. One of the questions raised by oncologists is the efficacy of ICIs in patients with molecular driver alterations, especially when the possibilities of using molecularly targeted therapies are exhausted (e.g., due to resistance to tyrosine kinase inhibitors). There are studies investigating this problem, but it is still poorly described. Among probable immunotherapy' failures reasons, low immunogenicity of tumors with one driver mutation is listed. Nevertheless, in some cases, the therapy is efficient, and more research is required to establish the management of NSCLC patients with oncogenic driver abnormalities. The aim of this article is to review current discoveries in this matter.

Keywords: immune checkpoint inhibitor; immunotherapy; molecularly targeted therapy; non-small-cell lung cancer; oncogenic driver alteration.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • B7-H1 Antigen / genetics
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors
  • Immunotherapy* / methods
  • Lung Neoplasms* / therapy
  • Male
  • Molecular Targeted Therapy*
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors
  • Protein Kinase Inhibitors

Grants and funding

This article received no external funding. Internal funding was received from Medical University of Lublin, Poland: Innovative grant (GI/3).