TY - JOUR
T1 - Distinct Mechanisms of Resistance to CDK4/6 Inhibitors Require Specific Subsequent Treatment Strategies
T2 - One Size Does Not Fit All
AU - Wingate, Hannah F.
AU - Keyomarsi, Khandan
N1 - Publisher Copyright:
© 2023 American Association for Cancer Research.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Cyclin-dependent kinase (CDK) 4/6 inhibitors have transformed the treatment landscape of patients with hormone receptor–positive breast cancers. However, despite improvements in clinical outcomes, the approximately 70% of patients with tumors that are not intrinsically resistant to a CDK4/6 inhibitor still ultimately acquire resistance, which leads to a dilemma for clinicians when deciding which treatment to offer patients when they demonstrate disease progression on a CDK4/6 inhibitor. As such, many groups have sought to understand the mechanisms of resistance to CDK4/6 inhibitors, mostly focusing on genetic alterations associated with resistance. Though several recurrent mutations have been described, they are not consistent enough to guide clinical practice or generate novel rational treatment options. Two recent publications have used transcriptomic analysis to unravel distinct mechanisms driving resistance to individual CDK4/6 inhibitors and in doing so have identified biomarkers that could potentially help identify the next course of treatment for patients following disease progression.
AB - Cyclin-dependent kinase (CDK) 4/6 inhibitors have transformed the treatment landscape of patients with hormone receptor–positive breast cancers. However, despite improvements in clinical outcomes, the approximately 70% of patients with tumors that are not intrinsically resistant to a CDK4/6 inhibitor still ultimately acquire resistance, which leads to a dilemma for clinicians when deciding which treatment to offer patients when they demonstrate disease progression on a CDK4/6 inhibitor. As such, many groups have sought to understand the mechanisms of resistance to CDK4/6 inhibitors, mostly focusing on genetic alterations associated with resistance. Though several recurrent mutations have been described, they are not consistent enough to guide clinical practice or generate novel rational treatment options. Two recent publications have used transcriptomic analysis to unravel distinct mechanisms driving resistance to individual CDK4/6 inhibitors and in doing so have identified biomarkers that could potentially help identify the next course of treatment for patients following disease progression.
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U2 - 10.1158/0008-5472.CAN-23-2608
DO - 10.1158/0008-5472.CAN-23-2608
M3 - Article
C2 - 37779425
AN - SCOPUS:85174641583
SN - 0008-5472
VL - 83
SP - 3165
EP - 3167
JO - Cancer Research
JF - Cancer Research
IS - 19
ER -