Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Abstract

Mitochondria are key regulators of cell survival and are involved in a plethora of mechanisms, such as metabolism, Ca2+ signaling, reactive oxygen species (ROS) production, mitophagy and mitochondrial transfer, fusion, and fission (known as mitochondrial dynamics). The tuning of these processes in pathophysiological conditions is fundamental to the balance between cell death and survival. Indeed, ROS overproduction and mitochondrial Ca2+ overload are linked to the induction of apoptosis, while the impairment of mitochondrial dynamics and metabolism can have a double-faceted role in the decision between cell survival and death. Tumorigenesis involves an intricate series of cellular impairments not yet completely clarified, and a further level of complexity is added by the onset of apoptosis resistance mechanisms in cancer cells. In the majority of cases, cancer relapse or lack of responsiveness is related to the emergence of chemoresistance, which may be due to the cooperation of several cellular protection mechanisms, often mitochondria-related. With this review, we aim to critically report the current evidence on the relationship between mitochondria and cancer chemoresistance with a particular focus on the involvement of mitochondrial dynamics, mitochondrial Ca2+ signaling, oxidative stress, and metabolism to possibly identify new approaches or targets for overcoming cancer resistance.

Development and Validation of a Novel Mitophagy-Related Gene Prognostic Signature for Hepatocellular Carcinoma Based on Immunoscore Classification of Tumor

“…Mitophagy accounts for the maintenance of cellular homeostasis and energy metabolism in cancers [ 13 ]. Despite efforts in investigating the role of mitophagy in cancer recurrence or acquired resistance anticancer therapeutics [ 14 , 15 ], the precise effect of mitophagy in predicting HCC patients' prognosis is still unknown. Herein, we combined MRGs with immunoscore-based tumor classification to construct a 9-gene risk signature for HCC.…”

Calix[4]arene chalcone amide C-1011 elicits differential effects on the viability of 4T1 mouse breast adenocarcinoma cells with different levels of adaptor protein Ruk/CIN85 expression

“…Like the cells that contain them, mitochondria are able to adapt to the tumor environment and are likely to evolve into "oncogenic mitochondria" capable of transmitting malignant properties to recipient cells. The broader search for cancer metabolic modulators has already identified therapies that target mitochondria in cancer cells, but the field is still in its infancy [15][16][17][18].…”

Development and validation of a prognostic model for mitophagy-related genes in colon adenocarcinoma: a study based on TCGA and GEO databases

“…Colon cancer has a high recurrence rate, short survival and poor quality of life [13], so the search for speci c and sensitive biomarkers is important [14]. While the role of mitophagy in carcinogenesis, tumor progression and anticancer therapy has been studied [8,15], the prognostic value of MRGs in COAD has not been systematically investigated. The risk model developed here can be validated by comparing OS and ROC curves between the training and validation sets (TCGA and GEO cohorts).…”