[PDF][PDF] Genomic aberrations that activate D-type cyclins are associated with enhanced sensitivity to the CDK4 and CDK6 inhibitor abemaciclib
X Gong, LM Litchfield, Y Webster, LC Chio, SS Wong… - Cancer cell, 2017 - cell.com
X Gong, LM Litchfield, Y Webster, LC Chio, SS Wong, TR Stewart, M Dowless, J Dempsey…
Cancer cell, 2017•cell.comMost cancers preserve functional retinoblastoma (Rb) and may, therefore, respond to
inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors
have shown promising clinical activity in breast cancer and lymphomas, but it is not clear
which additional Rb-positive cancers might benefit from these agents. No systematic survey
to compare relative sensitivities across tumor types and define molecular determinants of
response has been described. We report a subset of cancers highly sensitive to CDK4/6 …
inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors
have shown promising clinical activity in breast cancer and lymphomas, but it is not clear
which additional Rb-positive cancers might benefit from these agents. No systematic survey
to compare relative sensitivities across tumor types and define molecular determinants of
response has been described. We report a subset of cancers highly sensitive to CDK4/6 …
Summary
Most cancers preserve functional retinoblastoma (Rb) and may, therefore, respond to inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors have shown promising clinical activity in breast cancer and lymphomas, but it is not clear which additional Rb-positive cancers might benefit from these agents. No systematic survey to compare relative sensitivities across tumor types and define molecular determinants of response has been described. We report a subset of cancers highly sensitive to CDK4/6 inhibition and characterized by various genomic aberrations known to elevate D-cyclin levels and describe a recurrent CCND1 3′UTR mutation associated with increased expression in endometrial cancer. The results suggest multiple additional classes of cancer that may benefit from CDK4/6-inhibiting drugs such as abemaciclib.
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