Review structure‐ and dynamics‐based computational design of anticancer drugs

Abstract

Cancer is a class of highly complex diseases involving multiple genes and multiple cross-talks between signaling networks. Cancer cells may be developed from inherited defects or acquired damages of DNA. However, many cancers are resistant to treatment, and metastasis of cancers makes the disease even more intractable. Secondary malignancies are frequently observed after cancer chemotherapy. The call for more effective cancer therapy is obligatory. Using drug-cocktails that combine multiple anti-cancer agents working in different mechanisms has been a standard treatment of cancers to overcome the drug resistance problem. More recently, design of multiple ligands (may be more easily understood as "multiple target ligands"), i.e., single agents that target multiple biomolecules in a rational manner, receives increasing attention. For those who work on computational drug design, such tasks serve as new opportunities for achieving drugs with more effective pharmacological actions, in addition to designing compounds with better binding affinity, better selectivity, or to discovering compounds that can exert their actions allosterically. Some recent methodological developments on computational drug design are reviewed, and a few recent drug design efforts on a selected set of targets (topoisomerases, Ras proteins, protein kinases, and histone deacetylases) toward cancer treatment and cancer prevention are summarized.

Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy

“…Finally, recent pharmacology research has revealed the necessity to design compounds that act on multiple genes or molecular pathways. [14][15][16][17] In our study, we identified compounds targeting the differentiation of LUAD phenotypes, which may provide therapeutic targets for further analysis.…”

A Theoretical Approach for Understanding the Haze Phenomenon in Bottled White Wines at Molecular Level

“…The methods that are used in this research have been used intensively in drug design (Hellberg et al, 1987;Wishart et al, 2006;Matta & Boyd, 2007;Yuan et al, 2013;Distinto et al, 2015;Kristensen et al, 2015;Lin, 2016;Wang et al, 2016;Xiao et al, 2016), and it is hoped that their use in this field complements the experimental information from a new approach, favouring the holistic comprehension of the phenomenon.…”

Recent advances in radiotherapy and its associated side effects in cancer—a review

“…Secondary malignancies are the cancers occurring even after the initial treatment of the primary cancer. Radiotherapy with or without chemotherapy is a potential risk factor for secondary malignancies (Lin, 2016). Though ionizing radiations are used to destroy cancerous tissues, the incidence of second malignant neoplasm (SMN) arises among long-term survivors.…”