SF3b inhibitors suppress proliferation of nonsmall cell lung cancer cells irrespective of EGFR mutation status

SF3b inhibitors pladienolide B and herboxidiene suppress proliferation of NSCLC cell lines at 0.01 uM while increasing EGFR intron 2 retention in PC9, HCC827, and A549.

• Why it matters: EGFR-TKIs are standard for EGFR-mutant NSCLC, but acquired resistance limits durability, creating a need for therapies that do not rely on EGFR kinase activity.
• What they did: Three lung adenocarcinoma lines (PC9, HCC827, and A549) were treated with pladienolide B or herboxidiene at 0.01, 0.1, and 1 uM; proliferation was measured by crystal violet over three days, and EGFR intron 2 retention and EGFR protein were assessed by RTPCR and western blotting.
• The result: Both compounds increased intron 2 retained product in all three lines and held cell numbers near day 0 at concentrations down to 0.01 uM, with EGFR protein lost in PC9, reduced in A549, and only partly reduced in HCC827 despite full growth suppression.

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