Cancer Res Treat.  2022 Apr;54(2):315-329. 10.4143/crt.2022.078.

Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer

• Rivera-Concepcion J
• Uprety D
• Adjei AA

• KMID: 2528202
• DOI: http://doi.org/10.4143/crt.2022.078

Abstract

Precision oncology has fundamentally changed how we diagnose and treat cancer. In recent years, there has been a significant change in the management of patients with oncogene-addicted advanced-stage NSCLC. Increasing amounts of identifiable oncogene drivers have led to the development of molecularly targeted drugs. Undoubtedly, the future of thoracic oncology is shifting toward increased molecular testing and the use of targeted therapies. For the most part, these novel drugs have proven to be safe and effective. As with all great innovations, targeted therapies pose unique challenges. Drug toxicities, resistance, access, and costs are some of the expected obstacles that will need to be addressed. This review highlights some of the major challenges in the use of targeted therapies in NSCLC and provides guidance for the future strategies.

Keyword

Lung neoplasms; Non-small cell lung carcinoma; Targeted therapy; Challenges; Cost; Drug resistance; Toxicity

Figure

• 

  Fig. 1 Simplified diagram depicting various possible mechanisms of disease progression at a cellular-level following treatment with a tyrosine kinase inhibitor in oncogenic-addicted non–small cell lung cancer. Genetic mechanisms are further described in Fig. 2.

• 

  Fig. 2 Figure depicting signaling pathway in oncogenic-addicted non–small cell lung cancer (NSCLC) (A), mechanism of tyrosine kinase inhibitor (TKI) and various signaling pathways of disease resistance (B), including a gate-keeper mutation (C), bypass signaling (D) and a concurrent-driver oncogene (E). EGFR, epidermal growth factor receptor; MAPK, mitogen-activated protein kinase; NSCLC, non–small cell lung cancer; PI3K, phosphoinositide 3-kinase; TKI, tyrosine kinase inhibitor.

Reference

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