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Molecular Biomarkers Predictive of Resistance to CDK4/6


Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have revolutionized the treatment of hormone-positive metastatic breast cancers (mBCs). They are currently established as standard therapies in combination with endocrine therapy as first- and second-line systemic treatment options for both endocrine-sensitive and endocrine-resistant mBC populations. In the first-line metastatic setting, the median progression-free survival for the three currently approved CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, with aromatase inhibitors is greater than 2 years (palbociclib 27.6 months; ribociclib 25.3 months; and abemaciclib 28.18 months). Although CDK4/6 inhibitors have significant clinical benefits and enable physicians to delay starting chemotherapy, they are expensive and can be associated with drug toxicities. Here, we have performed a systemic review of the reported molecular markers predictive of drug response including intrinsic and acquired resistance for CDK4/6 inhibition in mBC. The rapidly emerging molecular landscape is captured through next-generation sequencing of breast cancers (DNA with or without RNA), liquid biopsies (circulating tumor DNA), and protein analyses. Individual molecular candidates with robust and reliable evidence are discussed in more depth.


  • Millie11
    Millie11 Member Posts: 4
    edited February 2022

    My oncologist wants to put me on one of these inhibitors when I finish chemo and radiation without first testing my cancer cells for the protein ki67. What if I don't have this protein in my cells how will this drug work for me?

    Anyone here been put on this CDK4/6 without first being tested for the protein ki-67 ?

  • nnguyen
    nnguyen Member Posts: 52
    edited February 2022

    Yes, my wife currently on Abemaciclib without first being tested for Ki67.Currently there are only 3 officially approved biomarkers to guide treatments for breast cancer, i.e ER, PR, and Her2. All the others (ki67, esr1, pik3__, PDL1, etc) might be used in clinical trials and definitely not in routine use.

    Incidentally, what made you asked about Ki67? From my next to nothing knowledge of Ki67, it might be a prognostic and proliferation indicator for certain group of breast cancer patients.