Rhabdomyolysis due to CDK4/6 inhibitor-statin interactions is a rare but potentially life-threatening complication. Vigilant monitoring, timely intervention, and tailored treatment strategies are essential for preventing complications and improving patient outcomes.

P2, N=32, Not yet recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

P=N/A, N=1342, Completed, Pfizer | N=733 --> 1342

We identified FDA-approved compounds acting through these pathways, three of which, Ribociclib, Ponatinib, and Dasatinib, showed superior efficacy to current therapies across renal cancer cell lines in preclinical screens. By acting through mechanisms distinct from current therapies, they represent promising candidates for combination strategies aimed at overcoming resistance and improving clinical outcomes in ccRCC.

This case highlights a rare but severe complication of ABE treatment. While CDK4/6 inhibitors are widely used as first-line agents in advanced breast cancer due to their high efficacy and generally favorable side-effect profile, clinicians should remain vigilant for NE, which requires prompt intervention.

We discuss the case literature on the management of ophthalmic and eyelid metastases, including the role of radiotherapy. We outline the multi-disciplinary team (MDT) discussions and recommendations made in the present case, which ultimately found that the risks of radiation toxicity would outweigh the benefits. Adjuvant therapy with fulvestrant and palbociclib was recommended, with future consideration of a CDK 4/6 inhibitor in the event of metastatic recurrence.

A 52-year-old woman with de novo metastatic, grade 1, luminal A ILC (ER+/PR+, HER2 0; Ki-67 5%) diagnosed in 2022 achieved durable disease control with systemic therapy and maintenance ribociclib plus ovarian suppression...Despite no clear radiologic progression on CT, symptomatic gastric involvement and weight loss prompted initiation of second-line weekly paclitaxel. Signet ring morphology in gastric biopsies is not pathognomonic for primary gastric carcinoma. In patients with current or prior ILC, an IHC panel incorporating breast-lineage markers (e.g., GATA3, TRPS1) and GI markers (e.g., CDX2, CK20), alongside E-cadherin status, is pivotal to avoid misdiagnosis, inappropriate surgery, and delay of systemic therapy.

The clinical deployment of ATP-competitive inhibitors-Palbociclib, Ribociclib, and Abemaciclib-has revolutionized the standard of care for hormone receptor-positive breast cancer. By recruiting the ubiquitin-proteasome system to catalytically degrade target proteins, CDK4/6-PROTACs eliminate both enzymatic activity and non-catalytic scaffolding functions, offering a mechanistically distinct strategy to overcome the structural limitations of traditional inhibitors. This review summarizes the progression from clinical inhibitors to strategies for overcoming resistance, offering insights into the future development of CDK4/6-targeted therapies.

Our findings revealed a signalling pathway in which lung adenocarcinoma regulates stemness and tumourigenesis through HES1, and the targeting of this pathway by VR23 or napabucasin supports further preclinical development for CDK4/6 inhibitor combination therapy.

High-resolution lineage tracing and multi-omic studies demonstrate that CDK4/6i resistance is shaped by clonal selection and adaptive remodeling of cell states, with the ESR1 mutation status and the specific inhibitor acting as key determinants of evolutionary trajectories. These findings suggest that both variables should be considered when designing sequential and combination treatment strategies to overcome CDK4/6i resistance.

Treating stage II and III HR + HER2 - breast cancer patients with CDK4/6 inhibitors in Austria reduces metastatic breast cancer recurrences, resulting in considerable medical benefits and economic effects.