Yet another process of G2 arrest is supplied by stress as described earlier, induced activation of p38 MAPK/MK2 and subsequent inactivation of CDC25B/C. By inducing the transcription of p21 and other proteins, p53 also plays a part within the G2 checkpoint. Cancer cells are dependent on the S and G2 checkpoints for repair of DNA damage, as a result of presence of faulty G1 checkpoint mechanisms. Afatinib clinical trial Because the S stage checkpoint facilitates slowing, instead of arrest, of the cell cycle, a cancer cell harbouring DNA damage might progress through the S checkpoint, simply to cease in the G2 checkpoint. Thus, the G2 checkpoint is just a critical guardian of the cancer cell genome, and it has emerged as a stylish therapeutic target for anti-cancer treatment. G2 abrogation stops cancer cells from repairing DNA damage, pushing them in to M phase and the so called mitotic catastrophe and apoptosis. The best G2 checkpoint abrogator will be selective, targeting a molecule not involved in G1 checkpoint or S cycle checkpoint Gene expression or, if involved, in a fashion. Choice objectives for G2 abrogation are discussed below. ATM/ATR inhibition Ataxia telangiectasia mutated and ATR stimulate pathways involved with apoptosis, cell cycle check-points, and DNA repair, therefore, they’re perhaps not unique G2 checkpoint abrogators. Nevertheless, coffee, which has several molecular effects, including ATR inhibition and ATM, has been shown to potentiate the cytotoxicity of nitrogen mustard by disrupting the G2 checkpoint, inducing damaged cells to undergo mitosis before effectively fixing lesions in their DNA. A less-toxic derivative of coffee, pentoxifylline, is tested AG-1478 solubility in clinical trials, however, its effects on cell biology can also be nonspecific. More certain ATM inhibitors are in development. Treatment of CDC25 and WEE1 Another strategy to abrogate the G2 checkpoint is to trigger CDC25C phosphatase, together with DNA damage. Initiating this results in dephosphorylation and activation of cyclin B/CDK1, producing cell cycle progression to M phase. Thus far, no such activators have now been produced. An alternate approach to G2 abrogation is the inhibition of WEE1, a protein that opposes CDC25 activity by phosphorylating and inactivating cyclin/CDK processes. MK2 inhibition The p38 MAPK/MK2 route is implicated in several cancer cell pathways, from those associated with progress, infection, replication, apoptosis, angiogenesis, and metastasis. Now, this process is found to be a regulator of checkpoint controls, particularly in the G2/M transition.