Computer-aided drug repurposing for cancer therapy: Approaches and opportunities to challenge anticancer targets

Despite huge efforts made in academic and pharmaceutical worldwide research, current anticancer therapies achieve effective treatment in a limited number of neoplasia cases only. Oncology terms such as big killers to identify tumours with yet a high mortality rate or undruggable cancer targets, and chemoresistance, represent the current therapeutic debacle of cancer treatments. In addition, metastases, tumour microenvironments, tumour heterogeneity, metabolic adaptations, and immunotherapy resistance are essential features controlling tumour response to therapies, but still, lack effective therapeutics or modulators. In this scenario, where the pharmaceutical productivity and drug efficacy in oncology seem to have reached a plateau, the so-called drug repurposing i.e. the use of old drugs, already in clinical use, for a different therapeutic indication is an appealing strategy to improve cancer therapy. Opportunities for drug repurposing are often based on occasional observations or on time-consuming pre-clinical drug screenings that are often not hypothesis-driven. In contrast, in-silico drug repurposing is an emerging, hypothesis-driven approach that takes advantage of the use of big data. Indeed, the extensive use of-omics technologies, improved data storage, data meaning, machine learning algorithms, and computational modeling all offer unprecedented knowledge of the biological mechanisms of cancers and drugs' modes of action, providing extensive availability for both disease-related data and drugs-related data. This offers the opportunity to generate, with time and cost-effective approaches, computational drug networks to predict, in-silico, the efficacy of approved drugs against relevant cancer targets, as well as to select better responder patients or disease' biomarkers. Here, we will review selected disease-related data together with computational tools to be exploited for the insilico repurposing of drugs against validated targets in cancer therapies, focusing on the oncogenic signaling pathways activation in cancer. We will discuss how in-silico drug repurposing has the promise to shortly improve our arsenal of anticancer drugs and, likely, overcome certain limitations of modern cancer therapies against old and new therapeutic targets in oncology.

Automated summary

Despite extensive efforts in academic and pharmaceutical research, current anticancer therapies have limited efficacy, with challenges such as chemoresistance and tumor heterogeneity. Drug repurposing, particularly in-silico approaches utilizing big data, offers a promising strategy to improve cancer therapy by predicting drug efficacy and selecting better responder patients. This method has the potential to overcome limitations of modern cancer therapies against both old and new therapeutic targets in oncology.