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Anti-Angiogenic Therapy in ALK Rearranged Non-Small Cell Lung Cancer (NSCLC)

Aaron C Tan1,2, Nick Pavlakis3,4

  • 1Division of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore.

International Journal of Molecular Sciences
|August 26, 2022
PubMed

Insights

Advanced lung cancer treatment is improving with targeted therapies like ALK tyrosine kinase inhibitors (TKI). This review explores anti-angiogenic therapy as a potential new option for ALK-rearranged non-small cell lung cancer (NSCLC) when resistance develops.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Advanced non-small cell lung cancer (NSCLC) management has improved with targeted therapies.
  • Anaplastic lymphoma kinase (ALK) gene rearrangements are key drivers in a subset of NSCLC.
  • ALK tyrosine kinase inhibitors (TKIs) are effective first-line treatments, but drug resistance is a significant challenge.

Purpose of the Study:

  • To review the current evidence and future directions for anti-angiogenic therapy in ALK-rearranged NSCLC.
  • To explore the potential of targeting the vascular endothelial growth factor (VEGF) pathway in overcoming ALK TKI resistance.
  • To discuss the pre-clinical rationale and clinical trial data for anti-angiogenic strategies in this patient population.

Main Methods:

  • Literature review of pre-clinical studies.
  • Analysis of clinical trial data investigating anti-angiogenic agents in NSCLC.
  • Synthesis of evidence regarding combination therapies involving anti-angiogenic agents and ALK TKIs.

Main Results:

  • ALK TKIs show survival benefits in advanced ALK-rearranged NSCLC, but resistance limits long-term efficacy.
  • Anti-angiogenic therapy has demonstrated efficacy in other NSCLC subtypes, often in combination regimens.
  • The role and optimal use of anti-angiogenic therapy in ALK-rearranged NSCLC are not yet fully established.

Conclusions:

  • Despite advances, treatment options for advanced ALK-rearranged NSCLC after TKI failure are limited.
  • Further research is warranted to evaluate the efficacy and safety of anti-angiogenic therapy in this setting.
  • Combination strategies may hold promise for improving outcomes in patients with resistant ALK-rearranged NSCLC.
Keywords:
ALK rearrangementanaplastic lymphoma kinaseanti-angiogenesisnon-small cell lung cancervascular endothelial growth factor

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