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Placenta-specific 8 is a potential novel target for osimertinib resistance in non-small cell lung cancer

Xiaoyun Fei1, Gang Wang2, Hui Shen1

  • 1Department of Respiratory Medicine, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.

Oncology Letters
|July 11, 2019
PubMed

Insights

Placenta-specific 8 (PLAC8) overexpression promotes resistance to osimertinib (AZD9291) in non-small cell lung cancer (NSCLC). Targeting PLAC8 may help overcome this drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osimertinib (AZD9291), a third-generation EGFR-TKI, treats NSCLC with EGFR T790M mutations.
  • Acquired resistance to osimertinib is a significant clinical challenge.
  • Placenta-specific 8 (PLAC8) is implicated in tumor progression and resistance, but its role in osimertinib resistance is unclear.

Purpose of the Study:

  • To investigate the functional role of PLAC8 in osimertinib (AZD9291) resistance in non-small cell lung cancer (NSCLC).

Main Methods:

  • Comparison of PLAC8 levels in AZD9291-resistant and parent NSCLC cells.
  • Overexpression of PLAC8 in parent NSCLC cells to assess drug sensitivity, proliferation, colony formation, and migration.
  • Analysis of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) levels in resistant and PLAC8-overexpressing cells.

Main Results:

  • PLAC8 levels were significantly upregulated in AZD9291-resistant NSCLC cells.
  • Overexpression of PLAC8 in parent cells reduced sensitivity to AZD9291 and enhanced proliferation, colony formation, and migration.
  • ALDH1A1 levels were also upregulated in resistant and PLAC8-overexpressing cells, suggesting its involvement.

Conclusions:

  • PLAC8 overexpression contributes to NSCLC resistance to AZD9291.
  • PLAC8 is a potential therapeutic target for overcoming AZD9291 resistance in NSCLC.
Keywords:
aldehyde dehydrogenase 1 family member A1non-small cell lung cancerosimertinib resistanceplacenta-specific 8

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