Morrison, L., Loibl, S. & Turner, N. C. The CDK4/6 inhibitor revolution—a game-changing era for breast cancer treatment. Nat. Rev. Clin. Oncol. 21, 89–105 (2024).
Article CAS PubMed Google Scholar
Hortobagyi, G. N. et al. A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial. Ann. Oncol. 36, 149–157 (2025).
Article CAS PubMed Google Scholar
O’Leary, B. et al. The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov. 8, 1390–1403 (2018).
Article PubMed PubMed Central Google Scholar
Wander, S. A. et al. The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors in patients with hormone receptor-positive metastatic breast cancer. Cancer Discov. 10, 1174–1193 (2020).
Article CAS PubMed PubMed Central Google Scholar
Gong, X. et al. Genomic aberrations that activate D-type cyclins are associated with enhanced sensitivity to the CDK4 and CDK6 inhibitor abemaciclib. Cancer Cell 32, 761–776 (2017).
Article CAS PubMed Google Scholar
Kudo, R. et al. Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion. Cancer Cell 42, 1919–1935 (2024).
Article CAS PubMed Google Scholar
Petroni, G., Buque, A., Zitvogel, L., Kroemer, G. & Galluzzi, L. Immunomodulation by targeted anticancer agents. Cancer Cell 39, 310–345 (2021).
Article CAS PubMed Google Scholar
Petroni, G., Formenti, S. C., Chen-Kiang, S. & Galluzzi, L. Immunomodulation by anticancer cell cycle inhibitors. Nat. Rev. Immunol. 20, 669–679 (2020).
Article CAS PubMed PubMed Central Google Scholar
Uzhachenko, R. V. et al. Metabolic modulation by CDK4/6 inhibitor promotes chemokine-mediated recruitment of T cells into mammary tumors. Cell Rep. 35, 108944 (2021).
Article CAS PubMed PubMed Central Google Scholar
Schmitt, C. A., Wang, B. & Demaria, M. Senescence and cancer—role and therapeutic opportunities. Nat. Rev. Clin. Oncol. 19, 619–636 (2022).
Article PubMed PubMed Central Google Scholar
Goel, S. et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature 548, 471–475 (2017).
Article CAS PubMed PubMed Central Google Scholar
Peuker, C. A. et al. Treatment with ribociclib shows favourable immunomodulatory effects in patients with hormone receptor-positive breast cancer—findings from the RIBECCA trial. Eur. J. Cancer 162, 45–55 (2022).
Article CAS PubMed Google Scholar
Togashi, Y., Shitara, K. & Nishikawa, H. Regulatory T cells in cancer immunosuppression—implications for anticancer therapy. Nat. Rev. Clin. Oncol. 16, 356–371 (2019).
Article CAS PubMed Google Scholar
Ali, L. R. et al. PD-1 blockade and CDK4/6 inhibition augment nonoverlapping features of T cell activation in cancer. J. Exp. Med. 220, e20220729 (2023).
Article CAS PubMed PubMed Central Google Scholar
Yuan, Y. et al. Phase I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer. Eur. J. Cancer 154, 11–20 (2021).
Article CAS PubMed PubMed Central Google Scholar
Petroni, G. et al. Radiotherapy delivered before CDK4/6 inhibitors mediates superior therapeutic effects in ER+ breast cancer. Clin. Cancer Res. 27, 1855–1863 (2021).
Article CAS PubMed PubMed Central Google Scholar
Petroni, G., Cantley, L. C., Santambrogio, L., Formenti, S. C. & Galluzzi, L. Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer. Nat. Rev. Clin. Oncol. 19, 114–131 (2022).
Article CAS PubMed Google Scholar
Petroni, G., Buqué, A., Coussens, L. M. & Galluzzi, L. Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment. Nat. Rev. Drug Discov. 21, 440–462 (2022).
Article CAS PubMed Google Scholar
De Angelis, C. et al. Activation of the IFN signaling pathway is associated with resistance to CDK4/6 inhibitors and immune checkpoint activation in ER+ breast cancer. Clin. Cancer Res. 27, 4870–4882 (2021).
Article PubMed PubMed Central Google Scholar
Teh, J. L. F. & Aplin, A. E. Arrested developments: CDK4/6 inhibitor resistance and alterations in the tumor immune microenvironment. Clin. Cancer Res. 25, 921–927 (2019).
Article CAS PubMed Google Scholar
Buque, A. et al. Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer. Nat. Commun. 11, 3819 (2020).
Article CAS PubMed PubMed Central Google Scholar
Alamilla-Presuel, J. C., Burgos-Molina, A. M., González-Vidal, A., Sendra-Portero, F. & Ruiz-Gómez, M. J. Factors and molecular mechanisms of radiation resistance in cancer cells. Int. J. Radiat. Biol. 98, 1301–1315 (2022).
Article CAS PubMed Google Scholar
Beringer, A. & Miossec, P. Systemic effects of IL-17 in inflammatory arthritis. Nat. Rev. Rheumatol. 15, 491–501 (2019).
Gelderblom, H. et al. Long-term outcomes of pexidartinib in tenosynovial giant cell tumors. Cancer 127, 884–893 (2021).
Article CAS PubMed Google Scholar
Buque, A. et al. Impact of radiation therapy dose, fractionation, and immunotherapeutic partner in a mouse model of hormone receptor-positive mammary carcinogenesis. J. Natl Cancer Inst. 117, 934–947 (2025).
Buqué, A. & Galluzzi, L. Modeling tumor immunology and immunotherapy in mice. Trends Cancer 4, 599–601 (2018).
Rugo, H. S. et al. Safety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Clin. Cancer Res. 24, 2804–2811 (2018).
Article CAS PubMed Google Scholar
Petroni, G. & Galluzzi, L. Impact of treatment schedule on the efficacy of cytostatic and immunostimulatory agents. Oncoimmunology 10, 1889101 (2021).
Article PubMed PubMed Central Google Scholar
Guo, S., Jiang, X., Mao, B. & Li, Q. X. The design, analysis and application of mouse clinical trials in oncology drug development. BMC Cancer 19, 718 (2019).
Article PubMed PubMed Central Google Scholar
Heckler, M. et al. Inhibition of CDK4/6 promotes CD8 T-cell memory formation. Cancer Discov. 11, 2564–2581 (2021).
Article CAS PubMed PubMed Central Google Scholar
Teh, J. L. F. et al. Activation of CD8+ T cells contributes to antitumor effects of CDK4/6 inhibitors plus MEK inhibitors. Cancer Immunol. Res. 8,
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