H1Innovative approaches to combat anti-cancer drug resistance: Targeting lncRNA and autophagy

Clin Transl Med. 2023 Oct;13(10):e1445. doi: 10.1002/ctm2.1445.

Abstract

Background: To date, standardizing clinical predictive biomarkers for assessing the response to immunotherapy remains challenging due to variations in personal genetic signatures, tumour microenvironment complexities and epigenetic onco-mechanisms.

Main body: Early monitoring of key non-coding RNA (ncRNA) biomarkers may help in predicting the clinical efficacy of cancer immunotherapy and come up with standard predictive ncRNA biomarkers. For instance, reduced miR-125b-5p level in the plasma of non-small cell lung cancer patients treated with anti-PD-1 predicts a positive outcome. The level of miR-153 in the plasma of colorectal cancer patients treated with chimeric antigen receptor T lymphocyte (CAR-T) cell therapy may indicate the activation of T-cell killing activity. miR-148a-3p and miR-375 levels may forecast favourable responses to CAR-T-cell therapy in B-cell acute lymphoblastic leukaemia. In cancer patients treated with the GPC3 peptide vaccine, serum levels of miR-1228-5p, miR-193a-5p and miR-375-3p were reported as predictive biomarkers of good response and improved overall survival. Therefore, there is a critical need for further studies to elaborate on the key ncRNA biomarkers that have the potential to predict early clinical responses to immunotherapy.

Conclusions: This review summarises important predictive ncRNA biomarkers that were reported in cancer patients treated with different immunotherapeutic modalities including monoclonal antibodies, small molecule inhibitors, cancer vaccines and CAR-T cells. In addition, a concise discussion on forthcoming perspectives is provided, outlining technical approaches for the optimal utilisation of immune-modulatory ncRNA biomarkers as predictive tools and therapeutic targets.

Keywords: apoptosis; autophagy; cancer; drug resistance; lncRNA.

Publication types

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

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Autophagy / genetics
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung*
  • Glypicans
  • Humans
  • Lung Neoplasms*
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • Receptors, Chimeric Antigen*
  • Tumor Microenvironment

Substances

  • RNA, Long Noncoding
  • Receptors, Chimeric Antigen
  • MicroRNAs
  • Biomarkers
  • Antineoplastic Agents
  • GPC3 protein, human
  • Glypicans
  • MIRN153 microRNA, human