Molecular Docking as a Therapeutic Approach for Targeting Cancer Stem Cell Metabolic Processes

Abstract

Cancer stem cells (CSCs) are subpopulation of cells which have been demonstrated in a variety of cancer models and involved in cancer initiation, progression, and development. Indeed, CSCs which seem to form a small percentage of tumor cells, display resembling characteristics to natural stem cells such as self-renewal, survival, differentiation, proliferation, and quiescence. Moreover, they have some characteristics that eventually can demonstrate the heterogeneity of cancer cells and tumor progression. On the other hand, another aspect of CSCs that has been recognized as a central concern facing cancer patients is resistance to mainstays of cancer treatment such as chemotherapy and radiation. Owing to these details and the stated stemness capabilities, these immature progenitors of cancerous cells can constantly persist after different therapies and cause tumor regrowth or metastasis. Further, in both normal development and malignancy, cellular metabolism and stemness are intricately linked and CSCs dominant metabolic phenotype changes across tumor entities, patients, and tumor subclones. Hence, CSCs can be determined as one of the factors that correlate to the failure of common therapeutic approaches in cancer treatment. In this context, researchers are searching out new alternative or complementary therapies such as targeted methods to fight against cancer. Molecular docking is one of the computational modeling methods that has a new promise in cancer cell targeting through drug designing and discovering programs. In a simple definition, molecular docking methods are used to determine the metabolic interaction between two molecules and find the best orientation of a ligand to its molecular target with minimal free energy in the formation of a stable complex. As a comprehensive approach, this computational drug design method can be thought more cost-effective and time-saving compare to other conventional methods in cancer treatment. In addition, increasing productivity and quality in pharmaceutical research can be another advantage of this molecular modeling method. Therefore, in recent years, it can be concluded that molecular docking can be considered as one of the novel strategies at the forefront of the cancer battle via targeting cancer stem cell metabolic processes.

Trends in metabolic signaling pathways of tumor drug resistance: A scientometric analysis

“…As we can see from the overall change tendency of burst keywords, the research hotspot has experienced a transition to precision cancer medicine. Besides, it’s interesting to note that three burst keywords including “tumor microenvironment” (2020–2022) ( 85 ), “invasion” (2019-2022) ( 108 ), and “target” (2019–2022) ( 109 ) are still ongoing. Metabolic signatures within the tumor microenvironment impact the immune function, therefore, overcoming individualized microenvironment-related resistance and identifying related novel targets and signatures will be research hotspots in the future ( 110 ).…”

Potential Benefits of Dietary Plant Compounds on Normal and Tumor Brain Cells in Humans: In Silico and In Vitro Approaches

“…Finally, the high efficacy in neuroblastoma of DNA-topoisomerase I inhibitors (e.g., camptotechin and its derivatives irinotecan and topotecan) was demonstrated decades ago [ 63 , 64 , 65 ]; at the same time, there were many chemical–chemical and chemical–natural combinations tested to manage tumor resistance or to obtain synergistic activity [ 66 , 67 , 68 ]. In addition, in silico studies have also revealed new molecular targets and tumor inhibitors as potential cancer approaches and combined therapies [ 69 , 70 , 71 ].…”

Metastasis and MAPK Pathways

“…The understanding of the complicated biology underpinning the survival strategy of cancer cells, especially CSCs following treatment with anticancer agents, is of particular importance. The understanding of signaling pathways involved in the acquisition of metastatic phenotype such as Hedgehog [ 71 , 91 ], NOTCH [ 92 , 93 ], WNT signaling [ 94 , 95 ], and pathways engaged in the proliferation and survival of cancer cells such as those exerted via stimulation of RTKs offers an opportunity to target cancer cells. Furthermore, cancer cells reprogram their metabolism to survive in the harsh conditions that they experience during metastatic processes.…”

“…There are numerous factors that influence the incidence of CSCs resistance. These include interactions of CSCs with microenvironment components, epigenetic alterations occurring in CSCs (disruptions in DNA methylation, nucleosome remodeling, histone modifications, and non-coding RNAs), enhanced drug efflux due to the upregulation of efflux proteins (such as glycoprotein P) and drug inactivating enzymes, enhanced DNA repair and the development of mechanisms that prevent apoptosis and induce quiescence or dormancy [ 91 ].…”