HR positive

Breast cancer cells (i.e., MCF7 and MDA-MB231) infected with a combination of recombinant HSV-1 viruses that express granulocyte-macrophage colony-stimulating factor (GM-CSF) and metformin exhibit a synergistic effect in promoting the expression of interferon-ϒ (IFN-ϒ) found within peripheral blood mononuclear cells (PBMCs) and exerting apoptotic and cytotoxic effects in the mentioned malignant cells. The online version contains supplementary material available at 10.1007/s12088-025-01523-7.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (such as palbociclib, ribociclib, and abemaciclib) exert their effects by arresting the cell cycle at the G1/S checkpoint. From the perspective of laboratory medicine, we further emphasize the importance of biomarker detection, therapeutic target assessment, and precision molecular subtyping in identifying patients most likely to benefit from CDK4/6 inhibitor-based therapies. In addition, we discuss the role of these agents in remodeling the TIME, evaluate current combination strategies aimed at overcoming resistance, and highlight future directions for advancing this rapidly evolving field.

Additionally, we uncovered a unique mechanism of clearance driven by both metabolism and efflux in rats and demonstrated that we could counter efflux-driven clearance with high permeability. Our efforts resulted in compound 19, which was potent against CDK2, exhibited good selectivity vs CDK4 and CDK1, and had pharmacokinetic properties that enabled evaluation in a CDK2 xenograft model of cancer, where it achieved nearly 80% tumor growth inhibition.

AI therapy is associated with significant and progressive endothelial dysfunction, which does not fully recover after treatment cessation, highlighting the importance of CV monitoring in patients receiving long-term AI therapy.

Cell viability was quantified using a tetrazolium-based colorimetric assay and apoptosis was evaluated by the Muse® Annexin V & Dead Cell assay based on Annexin V and 7-amino-actinomycin D staining; the expression levels of JNK, p38, ERK, beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), p62/sequestosome 1 (SQSTM1) and poly (ADP-ribose) polymerase (PARP) were assessed by western blotting. Pharmacological inhibition with SP600125 attenuated JNK phosphorylation, reduced apoptotic responses and diminished autophagy-associated marker accumulation, supporting the notion that JNK signaling contributes, at least in part, to these effects. These findings indicate that RTA-408 exerts nanomolar antiproliferative activity in both hormone receptor-positive and triple-negative BC cells through a JNK-dependent mechanism that simultaneously engages apoptosis and autophagy, supporting further in vivo and translational investigation.

Ribociclib-induced vitiligo-like depigmentation is an under-recognized adverse effect. Early recognition and multidisciplinary management are key to optimizing oncologic care without compromising therapeutic benefit.

Palestinian breast cancer is dominated by hormone-receptor-positive disease, but the combined HER2-positive fraction (21.8%) and triple-negative fraction (17.6%) together account for nearly two-fifths of cases - a higher burden of aggressive subtypes than is reported in most Western series. These findings underline the importance of universal IHC testing and targeted therapy access in Palestinian breast cancer care.

No statistically significant differences in ORR were detected according to prior CDK4/6 inhibitor exposure, number of prior treatment lines, or study design; however, these findings should be interpreted cautiously given the limited number of studies and substantial heterogeneity. Within a continuously evolving treatment landscape, further prospective studies are warranted to better define the optimal positioning of SG.

PD-L1 CN loss was associated with lower OS, particularly in HR(+) and HER2(-) patients. This result revealed the prognostic value of PD-L1 CNV in Indonesian advanced BC who received primary systemic therapy.

CDK4/6 inhibitor-based neoadjuvant therapy results in meaningful tumour downstaging and biological subtype modulation in HR+/HER2- breast cancer. The frequent conversion from Luminal B to Luminal A and the marked suppression of Ki-67 support the cytostatic, differentiation-driven mechanism of CDK4/6 inhibition. Although pCR rates remain modest compared with chemotherapy, the consistent biological and morphological responses highlight this approach as a lower-toxicity alternative or complement to chemotherapy in selected patients. Prospective studies incorporating proliferative dynamics and nodal outcomes are warranted.

BCL2 can serve as a useful prognostic marker and merits inclusion in the routine IHC panel for breast cancer, as it may contribute to the development of individualized, tailored therapeutic strategies.

 Switching CDK4/6i and ET conferred a statistically significant improvement of PFS in patients with progression or recurrence on prior CDK4/6i-containing therapy. These findings underscore the variability in survival outcomes based on post-CDK4/6i therapy choices in HR+/HER2- MBC, with promising evidence for rechallenging strategies.