Bioinformatics Infrastructure Facility, Department of Biochemistry, Centre of Excellence in Bioinformatics, University of Lucknow, Lucknow, Uttar Pradesh, India.
Institute for Development of Advanced Computing, ONGC Centre for Advanced Studies, University of Lucknow, Lucknow, Uttar Pradesh, India.
OMICS. 2019 Sep;23(9):417-425. doi: 10.1089/omi.2019.0095. Epub 2019 Jul 18.
Cancer and cardiovascular disease (CVD) have a common co-occurrence. Both diseases display overlapping pathophysiology and risk factors, suggesting shared biological mechanisms. Conditions such as obesity, diabetes, hypertension, smoking, poor diet, and inadequate physical activity can cause both heart disease and cancer. The burgeoning field of onco-cardiology aims to develop diagnostics and innovative therapeutics for both diseases through targeting shared mechanisms and molecular targets. In this overarching context, this expert review presents an analysis of the protein-protein interaction (PPI) networks for onco-cardiology drug discovery. Several PPI complexes such as MDM2-TP53 and CDK4-pRB have been studied for their tumor-suppressive functions. In addition, XIAP-SMAC, RAC1-GEF, Sur-2ESX, and TP53-BRCA1 are other PPI complexes that offer potential breakthrough for onco-cardiology therapeutics innovation. As both cancer and CVD share biological mechanisms to a certain degree, the PPI network analyses for onco-cardiology drug discovery are promising for addressing comorbid diseases in the spirit of systems medicine. We discuss the emerging architecture of PPI networks in cancer and CVD and prospects and challenges for their exploitation toward therapeutics applications. Finally, we emphasize that PPIs that were once thought to be undruggable have become potential new class of innovative drug targets.
癌症和心血管疾病（CVD）共同发生。这两种疾病表现出重叠的病理生理学和危险因素，表明存在共同的生物学机制。肥胖、糖尿病、高血压、吸烟、不良饮食和缺乏体育活动等情况会导致心脏病和癌症。肿瘤心脏病学这一新兴领域旨在通过针对共同机制和分子靶点，为这两种疾病开发诊断和创新疗法。在这个总体背景下，本专家评论对肿瘤心脏病学药物发现中的蛋白质-蛋白质相互作用（PPI）网络进行了分析。已经研究了几种 PPI 复合物，例如 MDM2-TP53 和 CDK4-pRB，以研究其肿瘤抑制功能。此外，XIAP-SMAC、RAC1-GEF、Sur-2ESX 和 TP53-BRCA1 是其他 PPI 复合物，为肿瘤心脏病学治疗创新提供了潜在突破。由于癌症和 CVD 在一定程度上具有共同的生物学机制，因此肿瘤心脏病学药物发现中的 PPI 网络分析有望在系统医学的精神下解决共病问题。我们讨论了癌症和 CVD 中新兴的 PPI 网络架构及其在治疗应用方面的前景和挑战。最后，我们强调，曾经被认为不可成药的 PPI 已成为潜在的新型创新药物靶标。
