Asati Vivek, Bharti Sanjay K, Mahapatra Debarshi Kar, Asati Vikas, Budhwani Ashok K
Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, India.
Curr Pharm Des. 2016;22(39):6039-6054. doi: 10.2174/1381612822666160614000053.
PIK3CA gene was found in generation of p110 alpha (p110α) protein through an instruction process. p110 alpha acts as a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) proceed phosphorylation of signal molecules through PI3K pathway. This PI3K involved in regulation of cellular growth, transformation, adhesion, apoptosis, survival and motility. In some situations the PI3K/Akt pathway get altered due to mutation in PIK3CA gene produced oncogenic event in human malignancy.
The goal of this work is to describe the PI3K signaling pathway including mutational activation of PIK3CA gene and inhibitors have been developed or under clinical trials for the targeting of PI3K or PI3KR kinases.
Various inhibitors such as Morpholine, pyrimidines, benzenesulfonamide, pyridopyrimidinone, imidazo[1,5]naphthyridine, benzeneacylhydrazones, thienopyrimidine, aminopyridopyrimidine, imidazopyridine, imidazo[1,2-a]pyridine, thiazolopyrimidinone, quinolines and quinoxalines, thieno[3,2-b]pyran-7-one, morpholino-1,3-benzoxazines, quinalozinones, pyrido [3,2-d]pyrimidines, benzo[d]thiazol-2-yl)acetamide, aminopyrimidines, chalcone , azaindole, pyrazolopyrimidine and pyridine, thienobenzoxepin, phenylquinazolines , pyrazolo[1,5-a]pyridines , imidazolo-pyrimidine etc. were investigated under laboratory level as PI3K inhibitors in which few having PI3K and mTOR dual inhibitory activities.
After a long term of prognostic standpoint, PIK3CA mutations discussed as a major target for various cancers. These PIK3CA mutations were found in various exon including 1,2,4,6,7,9,13,18 and 20 which may be a cause of different cancers such as breast, colon, ovarian, gastric, brain, lung etc. In clinical trials these mutations still remain question marks for presence or absence to the scientist regarding future perspective. The opinion of these studies is to development of more specific inhibitors of PI3K pathway which produce tremendous impact on various cancers developed due to PIK3CA mutations.
PIK3CA基因通过一个指令过程产生p110α蛋白。p110α作为磷脂酰肌醇3激酶（PI3K）的催化亚基，通过PI3K途径对信号分子进行磷酸化。该PI3K参与细胞生长、转化、黏附、凋亡、存活和运动的调节。在某些情况下，PI3K/Akt途径因PIK3CA基因突变而改变，在人类恶性肿瘤中引发致癌事件。
本研究的目的是描述PI3K信号通路，包括PIK3CA基因的突变激活，以及已开发或正在进行临床试验的针对PI3K或PI3KR激酶的抑制剂。
在实验室水平上研究了各种抑制剂，如吗啉、嘧啶、苯磺酰胺、吡啶并嘧啶酮、咪唑并[1,5]萘啶、苯甲酰腙、噻吩并嘧啶、氨基吡啶并嘧啶、咪唑吡啶、咪唑并[1,2-a]吡啶、噻唑并嘧啶酮、喹啉和喹喔啉、噻吩并[3,2-b]吡喃-7-酮、吗啉基-1,3-苯并恶嗪、喹那唑啉酮、吡啶并[3,2-d]嘧啶、苯并[d]噻唑-2-基）乙酰胺、氨基嘧啶、查耳酮、氮杂吲哚、吡唑并嘧啶和吡啶、噻吩并苯并氧杂卓、苯基喹唑啉、吡唑并[1,5-a]吡啶、咪唑并嘧啶等作为PI3K抑制剂，其中少数具有PI3K和mTOR双重抑制活性。
从长期预后的角度来看，PIK3CA突变被认为是各种癌症的主要靶点。这些PIK3CA突变存在于包括1、2、4、6、7、9、13、18和20在内的多个外显子中，可能是乳腺癌、结肠癌、卵巢癌、胃癌、脑癌、肺癌等不同癌症的病因。在临床试验中，这些突变对于科学家而言，在未来前景方面是否存在仍然是个问号。这些研究的观点是开发更特异性的PI3K途径抑制剂，这将对因PIK3CA突变而发生的各种癌症产生巨大影响。
