AI Article Synopsis
- Small cell lung cancer (SCLC) has high variability in its growth patterns and a poor prognosis mainly due to rapid chemotherapy resistance.
- Through bioinformatic analyses, researchers found that different SCLC cell phenotypes show varying sensitivities to chemotherapy, with certain growth patterns linked to increased resistance.
- The study identified that the activation of the PI3K/Akt/mTOR pathway is a key factor in this process, suggesting that combining chemotherapy with inhibitors of this pathway could enhance treatment effectiveness for SCLC.
Article Abstract
Small cell lung cancer (SCLC) is a phenotypically heterogeneous disease with an extremely poor prognosis, which is mainly attributed to the rapid development of resistance to chemotherapy. However, the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear. Through comprehensive bioinformatic analyses, we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy. Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant. Mechanistically, activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance. Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors. Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance, which holds important clinical implications for improving SCLC treatment.
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| http://dx.doi.org/10.1016/j.jgg.2021.04.001 | DOI Listing |
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