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Review
. 2020 Jun 15;12(6):1587.
doi: 10.3390/cancers12061587.

Current Strategies for Treating NSCLC: From Biological Mechanisms to Clinical Treatment

Junnan Li  1 , Hang Fai Kwok  1   2
Affiliations
Review

Current Strategies for Treating NSCLC: From Biological Mechanisms to Clinical Treatment

Junnan Li et al. Cancers (Basel). .

Abstract

The identification of specific epidermal growth factor receptor (EGFR)-activating mutations heralded a breakthrough in non-small-cell lung cancer (NSCLC) treatments, with the subsequent development of EGFR-tyrosine kinase inhibitor (TKIs) becoming the first-line therapy for patients harboring EGFR mutations. However, acquired resistance to EGFR-TKIs inevitably occurs in patients following initial TKI treatment, leading to disease progression. Various mechanisms are behind the acquired resistance, and mainly include (1) target gene modification, (2) alternative parallel pathway activation, (3) downstream pathway activation, and (4) histological/phenotypic transformation. Approaches to combat the acquired resistance have been investigated according to these mechanisms. Newer generations of TKIs have been developed to target the secondary/tertiary EGFR mutations in patients with acquired resistance. In addition, combination therapies have been developed as another promising strategy to overcome acquired resistance through the activation of other signaling pathways. Thus, in this review, we summarize the mechanisms for acquired resistance and focus on the potential corresponding therapeutic strategies for acquired resistance.

Keywords: EGFR mutation; combination targeted therapy; drug resistance mechanism; lung cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The molecular mechanisms for acquired resistance. The mechanisms include target gene modification, alternative parallel pathway activation, downstream pathway activation, and histological/phenotypic transformation. Both the amplification and mutations of receptor tyrosine kinases (RTKs) can induce downstream survival signaling pathways. Moreover, the direct overexpression and/or mutations of components of downstream pathways can also contribute to acquired resistance by assisting tumor cell survival. These mechanisms provide potential targets for combination strategies for treatment in cases of acquired resistance.
Figure 2
Figure 2
The relationship between miRNAs and epithelial–mesenchymal transition-inducing transcription factors (EMT-TFs).
See this image and copyright information in PMC

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