Protein kinases as signaling switchboards are frequently deregulated in cancer and signify vulnerable nodes and potential therapeutic targets. We here focus on the cell cycle kinase CDK6 and on the MAPK pathway and on their interplay.

Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have recently entered the therapeutic armamentarium of clinical oncologists, and show promising activity in patients with breast and other cancers.

Dec 8, 2023 · MEK and/or ERK inhibition increases CDK4i/6i efficacy against therapy naïve and CDK4i/6i-resistant AM cells in xenograft and patient-derived xenograft (PDX) models and promotes a defective DNA...

Nov 5, 2020 · Treatment with ERK1/2i+CDK4/6i significantly decreased the levels of p-Rb and E2F1, downstream targets of CDK4/6. Recent studies shown that, in addition to cell cycle regulation, CDK4 and CDK6 induce tumorigenesis through regulation of inflammatory cytokines that are induced via NFκB pathway activation.

Oct 23, 2023 · We employ a lysine-targeted sulfonyl fluoride probe, named XO44, which binds to 133 endogenous kinases in intact lenvatinib-resistant hepatocellular carcinoma (HCC) cells. This analysis reveals...

Jan 30, 2025 · Cyclin-dependent kinases (CDKs) 4 and 6 (CDK4/6) are important regulators of the cell cycle. Selective CDK4/6 small-molecule inhibitors have shown clinical activity in hormonal...

Jan 4, 2023 · Here, we found that concurrent treatment with both a CDK4/6 inhibitor (CDK4/6i) and an ERK-MAPK inhibitor (ERKi) synergistically suppresses the growth of PDAC cell lines and organoids by cooperatively blocking CDK4/6i-induced compensatory upregulation of ERK, PI3K, antiapoptotic signaling, and MYC expression.

5 days ago · Mitogenic signaling through the RAS-ERK and PI3K-mTOR networks leads to the upregulation of D-type Cyclins (Cyclins D1, D2, and D3), ... The knockdown of CDK6 sensitized melanoma cells to palbociclib, and binding was observed only when CDK6 was in its normal conformation, associated with the CDC37-HSP90 chaperone complex. ...

Jun 5, 2020 · CDK6 overexpression has been identified as a key determinant to confer acquired resistance to CDK4/6i, and Cornell et al. have reported that miR-432-5p suppresses the TGF-β pathway to promote CDK6 overexpression in ER + breast cancer cells .

The Ras-MEK-ERK axis is a signal transduction pathway that acts downstream of several receptors, contributing to the transcriptional and functional regulation of D-type cyclins and CDK4/6. Aberrant activation of Ras pathway plays a crucial role in malignant transformation, in a large number of human tumors.