To gain insight into the molecular implication of CDK2 and CDK4 kinases in psoriasis, we sought to characterize expression of these kinases and associated cyclins, as well as of CKIs, and addressed the status of CDK2 and CDK4 activity in human psoriatic epidermis.
The present study revealed that ERK1/2 signalling pathway with up-regulation of HRAS, ARAF, and MEK1 genes and up-regulation of positive regulators of cell cycle (CCND1, CDK4, and E2F1) and down-regulation negative regulators of cell cycle (CDKN2A, CDKN2B, and RB1) made highly dysregulated MAPK signalling pathway in parathyroid adenoma.
Overall, this study supports the concept that breast cancer patients with MMR deficiency as assessed by immunohistochemistry may be good candidates for alternative treatment approaches such as immune checkpoint or CDK4 inhibitors.
Proliferating cell nuclear antigen (PCNA)-, cyclin-dependent kinase 4 (CDK4)-, and Cyclin D1-positive podocytes were found in mice with adriamycin-induced nephropathy.
These include gene fusions in vascular neoplasms (FOSB, CAMTA1 and TFE3), round cell sarcomas (BCOR, DUX4 and WT1), and fibroblastic/myofibroblastic tumors (STAT6, ALK and Pan-TRK); amplifications in well-differentiated and dedifferentiated liposarcomas (MDM2 and CDK4); and deletions in several aggressive neoplasms (SMARCB1 and SMARCA4).
Patient quality of life is maintained under therapy and, particularly in later line settings, deterioration of quality of life is slowed down and symptoms such as pain are better controlled by CDK4/6i.
Ribociclib, an orally bioavailable small-molecule CDK4/6 inhibitor is currently undergoing evaluation to treat pediatric central nervous system (CNS) tumors.
These include gene fusions in vascular neoplasms (FOSB, CAMTA1 and TFE3), round cell sarcomas (BCOR, DUX4 and WT1), and fibroblastic/myofibroblastic tumors (STAT6, ALK and Pan-TRK); amplifications in well-differentiated and dedifferentiated liposarcomas (MDM2 and CDK4); and deletions in several aggressive neoplasms (SMARCB1 and SMARCA4).
These findings support a cooperative role for MAPK, PI3K, and cyclin-CDK4/6-INK4 signaling in the pathogenesis of histiocytic sarcoma and provide a rational basis for targeting these pathways.
Thus, combination of CDK4/6 and mTOR inhibitors might represent a novel, promising, and effective therapeutic approach against human ICC.<i>See related commentary by Malumbres, p. 6</i>.
Overexpression of TK1 and CDK9 in plasma-derived exosomes is associated with clinical resistance to CDK4/6 inhibitors in metastatic breast cancer patients.
Given that the treatment of patients with breast cancer brain metastases represents an area of unmet medical need, enrollment of patients with CNS metastases in ongoing clinical trials should be encouraged; innovative trials that examine response of CNS metastases to CDK4/6 inhibitors are also of interest.
Here, we show that palbociclib, a CDK4/6 inhibitor, can inhibit both progression of ductal carcinoma <i>in situ</i> (DCIS) and growth of invasive disease in both an ER(-) basal breast cancer model (MCFDCIS) and an ER(+) luminal model (MCF7 intraductal injection).
Our results suggest that the co-overexpression of MDM2 and CDK4, along with multiple genetic factors, increases the tendency for high-grade sarcoma with a DDLPS-like morphology in transformed human BMSCs by accelerating their growth and migration and blocking their adipogenic potential.
SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16<sup>INK4a</sup>-deficient profile associated with positive responses to CDK4/6 inhibitors.
Here, we show that palbociclib, a CDK4/6 inhibitor, can inhibit both progression of ductal carcinoma <i>in situ</i> (DCIS) and growth of invasive disease in both an ER(-) basal breast cancer model (MCFDCIS) and an ER(+) luminal model (MCF7 intraductal injection).