K Mangala Shenoy, Rathi Ekta, Udupa Karthik S, Prasada K Shama, Pai K Sreedhara Ranganath, Kini Suvarna Ganesh
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India.
Department of Medical Oncology, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India.
Curr Med Chem. 2025;32(6):1121-1143. doi: 10.2174/0109298673293028240326051835.
Ovarian cancer is one of the most familiar kinds of gynecological cancer seen in women. Though it is not as familiar as breast cancer, the survival rate for ovarian cancer is very low when compared with breast cancer. Even after being one among the familiar types, to date, there are no proper treatments available for ovarian cancer. All the treatments that are present currently show a high rate of recurrence after the treatment. Therefore, treating this silent killer from the roots is the need of the hour. PI3K/AKT/m-TOR pathway is one of the pathways that get altered during ovarian cancer. Studies are already going on for the inhibition of PI3K and mTOR separately. Efforts have been made to inhibit either PI3K or mTOR separately earlier. However, due to its side effects and resistance to the treatments available, current studies are based on the inhibition of PI3K and mTOR together. Inhibition of PI3K and mTOR simultaneously reduces the chances of negative feedback, thus decreasing the toxicity. This review contains the evolution of PI3K and mTOR drugs that are approved by the FDA and are in the trials for different cancer types, including ovarian cancer. In this article, how a molecular targeted therapy can be made successful and free from toxicity for treating ovarian cancer is discussed. Therefore, this review paves the way for finding an effective scaffold rather than the clinical part. The scaffold thus selected can be further modified and synthesized in the future as dual PI3K/mTOR inhibitors specifically for OC.
卵巢癌是女性中最常见的妇科癌症之一。尽管它不像乳腺癌那么为人熟知,但与乳腺癌相比,卵巢癌的生存率非常低。即使作为常见类型之一,迄今为止,卵巢癌仍没有合适的治疗方法。目前所有的治疗方法在治疗后都显示出很高的复发率。因此,从根本上治疗这个沉默的杀手是当务之急。PI3K/AKT/m-TOR信号通路是卵巢癌发生过程中发生改变的信号通路之一。目前已经在分别进行针对PI3K和mTOR的抑制研究。早期已经分别努力抑制PI3K或mTOR。然而,由于其副作用以及对现有治疗的耐药性,目前的研究基于同时抑制PI3K和mTOR。同时抑制PI3K和mTOR可减少负反馈的机会,从而降低毒性。这篇综述包含了已获美国食品药品监督管理局(FDA)批准以及正在针对包括卵巢癌在内的不同癌症类型进行试验的PI3K和mTOR药物的进展情况。在本文中,讨论了如何使分子靶向治疗成功且无毒性地治疗卵巢癌。因此,本综述为寻找有效的支架而非临床部分铺平了道路。如此选择的支架未来可进一步修饰并合成为专门用于卵巢癌的双PI3K/mTOR抑制剂。