Gaikwad Snehal M, Ray Pritha
Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre Navi Mumbai, Maharashtra, India.
Am J Nucl Med Mol Imaging. 2012;2(4):418-31. Epub 2012 Oct 15.
Platinum based drugs are widely used to treat various types of cancers by inducing DNA damage mediated cytotoxicity. However, acquirement of chemoresistance towards platinum based drugs is a common phenomenon and a major hurdle in combating the relapse of the disease. Oncogenesis and chemoresistance are multifactorial maladies which often involve deregulation of one of the prime cell survival pathways, the PI3K/Akt/mTOR signalling cascade. The genetic alterations related to this pathway are often responsible for initiation and/or maintenance of carcinogenesis. Molecular components of this pathway are long being recognized as major targets for therapeutic intervention and are now also have emerged as potential tools for diagnosis of cancer. To develop novel therapeutics against the key molecules of PI3K pathway, stringent validation is required using both in-vitro and in-vivo models. Repetitive and non-invasive molecular imaging techniques, a relatively recent field in biomedical imaging hold great promises for monitoring such diagnosis and therapy. In this review, we first introduced the PI3K/Akt/mTOR pathway and its role in acquirement of chemoresistance in various cancers. Further we described how non-invasive molecular imaging approaches are sought to use this PI3K signalling axis for the therapeutics and diagnosis. A theranostic approach using various imaging modalities should be the future of PI3K signalling based drug development venture.
铂类药物通过诱导DNA损伤介导的细胞毒性被广泛用于治疗各种类型的癌症。然而,对铂类药物产生化疗耐药性是一种常见现象,也是对抗疾病复发的主要障碍。肿瘤发生和化疗耐药是多因素疾病,通常涉及主要细胞存活途径之一PI3K/Akt/mTOR信号级联的失调。与该途径相关的基因改变通常是致癌作用起始和/或维持的原因。该途径的分子成分长期以来一直被认为是治疗干预的主要靶点,现在也已成为癌症诊断的潜在工具。为了开发针对PI3K途径关键分子的新型疗法,需要使用体外和体内模型进行严格验证。重复和非侵入性分子成像技术是生物医学成像中一个相对较新的领域,在监测此类诊断和治疗方面具有巨大潜力。在这篇综述中,我们首先介绍了PI3K/Akt/mTOR途径及其在各种癌症化疗耐药性获得中的作用。进一步,我们描述了如何寻求使用非侵入性分子成像方法利用这个PI3K信号轴进行治疗和诊断。使用各种成像方式的治疗诊断方法应该是基于PI3K信号的药物开发事业的未来。