Page 34 - TD-4-3

Tumor Discovery Immunomodulatory effects of CDK4/6 inhibitors

Large-scale, randomized, placebo-controlled phase III References
trials are necessary to confirm both the efficacy and 1. George MA, Qureshi S, Omene C, Toppmeyer DL,
safety profiles of these treatments. Patients whose tumors Ganesan S. Clinical and pharmacologic differences
develop resistance through immune evasion mechanisms of CDK4/6 inhibitors in breast cancer. Front Oncol.
may benefit more from the addition of ICIs. The gut 2021;11:693104.
microbiome may also play a role in predicting responses to doi: 10.3389/fonc.2021.693104
ICI combination therapies. Further research is needed to
95
identify specific biomarkers that can predict which patients 2. Schettini F, De Santo I, Rea CG, et al. CDK 4/6 inhibitors
will benefit most from this approach. as single agent in advanced solid tumors. Front Oncol.
2018;8:608.
8. Conclusion doi: 10.3389/fonc.2018.00608

CDK4/6 inhibitors modulate antitumor immunity through 3. Ye M, Xu H, Ding J, Jiang L. Therapy for hormone receptor-
multifaceted mechanisms, including direct regulation positive, human epidermal growth receptor 2-negative
of T-cell activity, remodeling of the immunosuppressive metastatic breast cancer following treatment progression via
TME, and regulation of immune checkpoint expression. CDK4/6 inhibitors: A literature review. Breast Cancer (Dove
Med Press). 2024;16:181-197.
These immunomodulatory effects provide a mechanistic
rationale for combining CDK4/6 inhibitors with ICIs, doi: 10.2147/BCTT.S438366
which may overcome resistance and amplify therapeutic 4. Iranzo P, Callejo A, Assaf JD, et al. Overview of checkpoint
efficacy in cancer treatment. Future studies should inhibitors mechanism of action: Role of immune-related
focus on elucidating the differential impacts of CDK4/6 adverse events and their treatment on progression of
inhibition across diverse immune cell populations, refining underlying cancer. Front Med (Lausanne). 2022;9:875974.
combinatorial strategies with immunotherapy, and doi: 10.3389/fmed.2022.875974
validating these observations across a broader spectrum of 5. Shiravand Y, Khodadadi F, Kashani SMA, et al. Immune
tumor malignancies. checkpoint inhibitors in cancer therapy. Current Oncol.
2022;29(5):3044-3060.
Acknowledgments
doi: 10.3390/curroncol29050247
None.
6. Nunes Filho P, Albuquerque C, Pilon Capella M, Debiasi M.
Funding Immune checkpoint inhibitors in breast cancer: A narrative
review. Oncol Ther. 2023;11(2):171-183.
None. doi: 10.1007/s40487-023-00224-9
Conflict of interest 7. Scirocchi F, Scagnoli S, Botticelli A, et al. Immune effects of
-
+
CDK4/6 inhibitors in patients with HR /HER2 metastatic
The authors declare they have no competing interests. breast cancer: Relief from immunosuppression is associated
with clinical response. EBioMedicine. 2022;79:104010.
Author contributions
doi: 10.1016/j.ebiom.2022.104010
Conceptualization: Jundong Wu, Chunfa Chen 8. Goel S, DeCristo MJ, Watt AC, et al. CDK4/6 inhibition triggers
Visualization: Bingfeng Chen, Chunfa Chen, Siyue Lin anti-tumour immunity. Nature. 2017;548(7668):471-475.
Writing – original draft: Yuling Zhang, Chunfa Chen,
Rendong Zhang doi: 10.1038/nature23465
Writing – review & editing: Jundong Wu, Chunfa Chen 9. Thu KL, Soria-Bretones I, Mak TW, Cescon DW. Targeting
the cell cycle in breast cancer: Towards the next phase. Cell
Ethics approval and consent to participate Cycle. 2018;17(15):1871-1885.
Not applicable. doi: 10.1080/15384101.2018.1502567
10. Stanciu IM, Parosanu AI, Orlov-Slavu C, et al. Mechanisms
Consent for publication of resistance to CDK4/6 inhibitors and predictive biomarkers
+
Not applicable. of response in HR /HER2-metastatic breast cancer-a review
of the literature. Diagnostics (Basel). 2023;13(5):987.
Availability of data doi: 10.3390/diagnostics13050987
Not applicable. 11. Goel S, DeCristo MJ, McAllister SS, Zhao JJ. CDK4/6

Volume 4 Issue 3 (2025) 26 doi: 10.36922/TD025190037