Grasping cryptic binding sites to neutralize drug resistance in the field of anticancer.

Drug resistance is a significant obstacle to successful cancer treatment. The utilization and development of cryptic binding sites (CBSs) in proteins involved in cancer-related drug-resistance (CRDR) could help to overcome that drug resistance. However, there is no comprehensive review of the successful use of CBSs in addressing CRDR. Here, we have systematically summarized and analyzed the opportunities and challenges of using CBSs in addressing CRDR and revealed the key role that CBSs have in targeting CRDR. First, we have identified the CRDR targets and the corresponding CBSs. Second, we discuss the mechanisms by which CBSs can overcome CRDR. Finally, we have provided examples of successful CBS applications in addressing CRDR. We hope that this approach will provide guidance to biologists and chemists in effectively utilizing CBSs for the development of new drugs to alleviate CRDR.

In silico resources help combat cancer drug resistance mediated by target mutations.

Drug resistance causes catastrophic cancer treatment failures. Mutations in target proteins with altered drug binding indicate a main mechanism of cancer drug resistance (CDR). Global research has generated considerable CDR-related data and well-established knowledge bases and predictive tools. Unfortunately, these resources are fragmented and underutilized. Here, we examine computational resources for exploring CDR caused by target mutations, analyzing these tools based on their functional characteristics, data capacity, data sources, methodologies and performance. We also discuss their disadvantages and provide examples of how potential inhibitors of CDR have been discovered using these resources. This toolkit is designed to help specialists explore resistance occurrence effectively and to explain resistance prediction to non-specialists easily.