Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with synovial proliferation and bone erosion, which leads to the structural and functional impairment of the joints. Immune cells, together with synoviocytes, induce a pro-inflammatory environment and novel treatment agents target inflammatory cytokines. Psoriasis is a chronic immune-mediated skin disease, and several cytokines are considered as typical mediators in the progression of the disease, including IL-23, IL-22, and IL-17, among others.
In this review, we try to evaluate whether cyclin-dependent kinases (CDK), enzymes that regulate cell cycle and transcription of various genes, could become novel therapeutic targets in RA and psoriasis. We present the main results of in vitro and in vivo studies, as well as scarce clinical reports.
CDK inhibitors seem promising for treating RA and psoriasis because of their multidirectional effects. CDK inhibitors may affect not only the process of osteoclastogenesis, thereby reducing joint destruction in RA, but also the process of apoptosis of neutrophils and macrophages responsible for the development of inflammation in both RA and psoriasis. However, assessing the efficacy of these drugs in clinical practice requires multi-center, long-term clinical trials evaluating the effectiveness and safety of CDK-blocking therapy in RA and psoriasis.

Recent evidence suggests that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors significantly improve progression-free survival and overall survival among metastatic breast cancer patients. However, given the effects on cell cycle arrest, there is potential for CDK4/6 inhibitors and radiotherapy (RT) to work synergistically, enhancing the effect and toxicities of RT. A comprehensive review of the literature on the combination of RT and CDK4/6 inhibitors was performed with 19 eligible studies included in the final analysis. A total of 373 patients who received radiotherapy combined with CDK4/6 inhibitors were evaluated across 9 retrospective studies, 4 case reports, 3 case series, and 3 letters to the editor. The CDK4/6 inhibitor used, RT target, and RT technique were assessed in terms of toxicities. This literature review demonstrates generally limited toxicities with the combination of CDK4/6 inhibitors and palliative radiotherapy to metastatic breast cancer patients. The current evidence is nonetheless limited, and further results of ongoing prospective clinical trials will help clarify whether these treatments can be safely combined.

Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics involving the induction of protein degradation. Cyclin-dependent kinase (CDK) protein, which is involved in cycles and transcription cycles, participates in regulation of the cell cycle, transcription and splicing. Proteolysis-targeting chimeras targeting CDKs show several advantages over traditional CDK small-molecule inhibitors in potency, selectivity and drug resistance. In addition, the discovery of molecule glues promotes the development of CDK degraders. Herein, the authors describe the existing CDK degraders and focus on the discussion of the structural characteristics and design of these degraders.

Resistance to endocrine treatment generally occurs over time, especially in the metastatic stage. In this paper, we aimed to review the mechanisms of cyclin-dependent kinase (CDK) 4/6 inhibition and clinical usage of new agents in the light of recent literature updates.
A literature search was carried out using PubMed, Medline and ASCO and ESMO annual-meeting abstracts by using the following search keywords; \"palbociclib\", \"abemaciclib\", \"ribociclib\", \"cyclin-dependent kinase inhibitors\" and \"CDK 4/6\" in metastatic breast cancer (MBC). The last search was on 10 June 2017.
CDKs and cyclins are two molecules that have a key role in cell cycle progression. Today, there are three highly selective CDK4/6 inhibitors in clinical development - palbociclib, ribociclib and abemaciclib. Palbociclib and ribociclib were recently approved by the US FDA in combination with letrozole for the treatment of MBC in a first-line setting, as well as palbociclib in combination with fulvestrant for hormone-receptor (HR)-positive MBC that had progressed while on previous endocrine therapy according to the PALOMA-1, MONALEESA-2 and PALOMA-3 trials, respectively. In the recently published randomized phase III MONARCH 2 trial, abemaciclib plus letrozole had longer progression-free survival and higher objective response rates with less serious adverse events in advanced HR-positive breast cancer previously treated with hormonal treatment.
CDK4/6 inhibition is a new and promising target for patients with hormone-receptor-positive MBC. Both palbociclib and ribociclib showed significant additive benefit for patients receiving first-line treatment for HR-positive, epidermal growth factor receptor-2-negative advanced breast cancer. Palbociclib and abemaciclib also had significant activity in combination with fulvestrant for patients with MBC that progressed on previous endocrine therapy.