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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application

Paolo Maione1, Paola Claudia Sacco2, Assunta Sgambato3

  • 1Division of Medical Oncology, 'S. G. Moscati' Hospital, Contrada Amoretta, Avellino, 83100, Italy.

Therapeutic Advances in Medical Oncology
|September 2, 2015
PubMed

Insights

Targeted therapies like EGFR and ALK inhibitors have revolutionized non-small cell lung cancer (NSCLC) treatment. Overcoming drug resistance with novel agents is crucial for improving patient outcomes in advanced NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Aberrant signaling pathways driven by druggable protein kinases are key in non-small cell lung cancer (NSCLC).
  • Tyrosine kinase inhibitors (TKIs) targeting Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) have transformed advanced NSCLC treatment.
  • First-generation TKIs show improved outcomes over chemotherapy in specific patient populations with NSCLC.

Purpose of the Study:

  • To review the impact of TKIs in advanced NSCLC.
  • To discuss mechanisms of acquired resistance to TKIs.
  • To highlight the development of novel TKI generations for overcoming resistance.

Main Methods:

  • Literature review of clinical trials and research on EGFR and ALK inhibitors in NSCLC.
  • Analysis of mechanisms underlying TKI resistance.
  • Evaluation of emerging novel generation TKIs.

Main Results:

  • First-generation TKIs offer significant benefits in selected NSCLC patients.
  • Acquired drug resistance remains a major challenge, developing through various mechanisms.
  • Novel generation EGFR and ALK inhibitors show promise in patients resistant to prior treatments.

Conclusions:

  • Targeted therapy with TKIs has significantly advanced NSCLC treatment.
  • Addressing and overcoming TKI resistance is a priority for further improving outcomes.
  • Continued research into new drugs and strategies is essential for managing advanced NSCLC.
Keywords:
ALK rearrangementsAZD9291CO-1686EGFR mutationsT790Malectinibceritinibselective EGFR inhibitors

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