In-Silico Methodologies for Cancer Multidrug Optimization
DOI:
https://doi.org/10.24297/ijct.v17i2.7168Keywords:
In silico methodologies, drug combination, cancer, pharmacogenomics, drug synergyAbstract
Drug combinations is considered as an effective strategy designed to control complex diseases like cancer. Combinations of drugs can effectively decrease side effects and enhance adaptive resistance. Therefore, increasing the likelihood of defeating complex diseases in a synergistic way. This is due to overcoming factors such as off-target activities, network robustness, bypass mechanisms, cross-talk across compensatory escape pathways and the mutational heterogeneity which results in alterations within multiple molecular pathways. The plurality of effective drug combinations used in clinic were found out through experience. The molecular mechanisms underlying these drug combinations are often not clear, which makes it not easy to suggest new drug combinations. Computational approaches are proposed to reduce the search space for defining the most promising combinations and prioritizing their experimental evaluation. In this paper, we review methods, techniques and hypotheses developed for in silico methodologies for drug combination discovery in cancer, and discuss the limitations and challenges of these methods.
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