Experimental study demonstrates that low CDK4 expression increases sensitivity to LEE011 in fusion-positive rhabdomyosarcoma, suggesting amplified tumors may resist CDK4/6 inhibition.
Our data demonstrate that CDK4 is necessary but overexpression is not sufficient for RB-E2F-mediated G1-phase cell-cycle progression, proliferation, and transformation in fusion-positive RMS. Our studies indicate that LEE011 is active in the setting of fusion-positive RMS and suggest that low CDK4-expressing fusion-positive tumors may be particularly susceptible to CDK4/6 inhibition.
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Olanich et al. (2015) studied this question.
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