New Insight to Overcome Tumor Resistance: An Overview from Cellular to Clinical Therapies
Source : https://www.mdpi.com/2075-1729/11/11/1131
Disease relapse caused by drug resistance still represents a major clinical hurdle in cancer treatments. Tumor cells may take advantage of different intracellular and genetic systems attenuating the drug effects. Resistant cells or minimal residual disease (MRD) cells have strong clinical relevance, as they might give rise to secondary tumors when the therapy is concluded.
Conclusion/Relevance: Resistant cells or minimal residual disease (MRD) cells have strong clinical relevance, as they might give rise to secondary tumors when the therapy is concluded. Thus, MRDs are crucial therapeutic targets in order to prevent tumor relapse. Therefore, several groups aim at understanding how MRDs are orginated, characterizing their molecular features, and eradicating them. In this review, we will describe MRD from a genetic, evolutionary, and molecular point of view. Moreover, we will focus on the new in vitro, in vivo, preclinical, and clinical studies that aim at eradicating tumor resistance.
• Source: Life
• Conclusion/Relevance: “In this review, we will describe MRD from a genetic, evolutionary, and molecular point of view. Moreover, we will focus on the new in vitro, in vivo, preclinical, and clinical studies that aim at eradicating tumor resistance.”
• The pathogenesis of MRD is only partly elucidated. Drug toxicity only somewhat impacts MRD viability, with effects attenuated by decreasing intracellular concentrations of the compound. MRD calls can evade the toxic effects of therapy by stymieing apoptosis or activating protection mechanisms, such as DNA repair. These cells could have mutations in p53 or BcD, thus blocking the apoptotic cascade.
• MRDs show some characteristics of cancer stem cells (CSCs), and like normal stem cells, they have self-renewal capabilities.
• “Analogously to MRD cells, CSCs upregulate cell pumps to efflux drug from the cells and have slower cell cycles,” wrote the authors. “Despite these two populations sharing commonalities, the extent of the similarity between MRD and CSCs and whether these populations actually overlap are still open questions. CSC identification was pivotal to study tumor architecture and organization. Similar to their normal counterparts, tumors are well-organized entities (sometimes hierarchically). This heterogeneity across cancer cells is one major hurdle to effective cancer therapy. As reported in different cancer types, tumor is not a single disease, but is composed by different cells possessing their own distinctive biological features.”