The cell cycle is controlled by numerous mechanisms ensuring correct cell division. This review will focus on these mechanisms, i.e. regulation of cyclin-dependent kinases (CDK) by cyclins, CDK inhibitors and phosphorylating events. The quality checkpoints activated after DNA damage are also discussed. The complexity of the regulation of the cell cycle is also reflected in the different alterations leading to aberrant cell proliferation and development of cancer. Consequently, targeting the cell cycle in general and CDK in particular presents unique opportunities for drug discovery. This review provides an overview of deregulation of the cell cycle in cancer. Different families of known CDK inhibitors acting by ATP competition are also discussed. Currently, at least three compounds with CDK inhibitory activity (flavopiridol, UCN-01, roscovitine) have entered clinical trials.
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http://dx.doi.org/10.1046/j.1365-2184.2003.00266.x | DOI Listing |
Blood
January 2025
Universitätsklinikum Heidelberg, Med. Klinik V, GMMG-Studygroup, Heidelberg, Germany.
The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months.
View Article and Find Full Text PDFBioconjug Chem
January 2025
Department of Biochemistry, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Torun, ul. Lwowska 1, 87-100 Torun, Poland.
l-Asparaginase (l-ASNase) catalyzes the hydrolysis of l-asparagine, leading to its depletion and subsequent effects on the cellular proliferation and survival. In contrast to normal cells, malignant cells that lack asparagine synthase are extremely susceptible to asparagine deficiency. l-ASNase has been successfully employed in treating pediatric leukemias and non-Hodgkin lymphomas; however, its usage in adult patients and other types of cancer is limited due to significant side effects and drug resistance.
View Article and Find Full Text PDFPLoS One
January 2025
Institute of Sport Sciences, Jerzy Kukuczka Academy of Physical Education in Katowice, Katowice, Poland.
Curcumin is known for its potential health benefits; however, the evidence remains inconclusive regarding its necessity as a supplement for athletes during the preparatory phase of training. This study aimed to assess the effect of 6-week curcumin supplementation at a dose of 2g/day on selected inflammatory markers, blood count, and brain-derived neurotropic factor (BDNF) levels in middle-aged amateur long-distance runners during the preparatory period of a macrocycle. Thirty runners were randomly assigned to either a curcumin-supplemented group (CUR, n = 15) or a placebo group (PLA, n = 15).
View Article and Find Full Text PDFPLoS One
January 2025
South African Grape and Wine Research Institute, Stellenbosch University, Stellenbosch, South Africa.
Hyphopichia pseudoburtonii, is emerging as a potential biocontrol agent against various phytopathogens. These traits have been attributed to the production of various antifungal compounds in the presence of target pathogens. However, the broad molecular mechanisms involved in the antifungal activity are not yet understood.
View Article and Find Full Text PDFMed Oncol
January 2025
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
5-FU is a widely used chemotherapy drug for esophageal carcinomas, but therapy failure has been observed in 5-FU-resistant patients. Overcoming this resistance is a significant challenge in cancer treatment, requiring identifying and targeting important resistance mechanisms. PYGO2 expression is crucial in developing resistance to various chemotherapy drugs.
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