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Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
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SHP2 Inhibition Benefits Epidermal Growth Factor Receptor-mutated Non-Small Cell Lung Cancer Therapy

Leiming Xia1, Lu Wen2, Siying Wang1

  • 1Basic College of Medicine, Anhui Medical University, Hefei, China.

Mini Reviews in Medicinal Chemistry
|November 27, 2020
PubMed

Insights

Targeting SHP2 (Src homology 2-containing phosphotyrosine phosphatase 2) may enhance epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) efficacy in non-small cell lung cancer (NSCLC). Combination therapy shows promise for overcoming resistance to EGFR-TKIs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) face challenges due to persistent EGFR mutations in non-small cell lung cancer (NSCLC).
  • SHP2 (Src homology 2-containing phosphotyrosine phosphatase 2) is implicated in cancer progression through hyperactivated intracellular pathways and cancer stemness.
  • SHP2's role in EGFR-mutated NSCLC pathways presents a potential therapeutic target.

Purpose of the Study:

  • To investigate the mechanisms of SHP2 in EGFR-mutated NSCLC.
  • To explore the potential synergistic effects of combining SHP2 inhibitors with EGFR-TKIs.
  • To evaluate SHP2 inhibition as a strategy to overcome EGFR-TKI resistance.

Main Methods:

  • Literature review and mechanistic analysis of SHP2's role in NSCLC.
  • Analysis of SHP2's involvement in EGFR downstream and independent pathways.
  • Exploration of SHP2's impact on cancer stemness.

Main Results:

  • SHP2 plays a critical role in regulating malignant biology in NSCLC, overlapping with EGFR downstream pathways.
  • SHP2 suppression has been shown to disrupt cancer stemness.
  • SHP2 inhibition may sensitize or synergistically enhance the anti-tumor efficacy of EGFR-TKIs.

Conclusions:

  • SHP2 inhibition is a potential therapeutic strategy to enhance EGFR-TKI effectiveness in EGFR-mutated NSCLC.
  • Combining SHP2 inhibitors with EGFR-TKIs could overcome treatment resistance and improve patient outcomes.
  • Targeting SHP2 offers a promising approach to address the limitations of current EGFR-TKI therapy in NSCLC.
Keywords:
EGFR-TKIsNSCLC.SHP2drug resistenceinhibitionmutation

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