Pharmacological targeting of mitochondria in cancer stem cells: An ancient organelle at the crossroad of novel anti-cancer therapies

Škoda, J.; Borankova, Karolina; Jansson, Patric J.; Huang, Michael L.H.; Veselská, Renata; Richardson, Des R.

doi:10.1016/j.phrs.2018.11.020

Cited by 59 publications

(59 citation statements)

References 244 publications

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“…Moreover, doxycycline has been used in a clinical pilot trial for the preoperative treatment of early breast cancer patients, leading to a statistically significant decrease in the stemness markers aldehyde dehydrogenase 1 and CD44 . This type of results has led to the suggestion that tetracyclines may specifically target cancer stem cells and hence could be “repurposed” for the treatment of neoplastic diseases …”

Section: Strategies For Oxphos Inhibitionmentioning

confidence: 99%

“…25 This type of results has led to the suggestion that tetracyclines may specifically target cancer stem cells and hence could be "repurposed" for the treatment of neoplastic diseases. 26 Cationic lipophils. Following the Nernst equation, cationic lipophilic molecules tend to enrich in the mitochondrial matrix driven by the mitochondrial inner transmembrane potential (ΔΨ m ).…”

Section: Strategies For Oxphos Inhibitionmentioning

confidence: 99%

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Oxidative phosphorylation as a potential therapeutic target for cancer therapy

Sica

Pedro

Stoll

et al. 2019

Intl Journal of Cancer

148

114

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In contrast to prior belief, cancer cells require oxidative phosphorylation (OXPHOS) to strive, and exacerbated OXPHOS dependency frequently characterizes cancer stem cells, as well as primary or acquired resistance against chemotherapy or tyrosine kinase inhibitors. A growing arsenal of therapeutic agents is being designed to suppress the transfer of mitochondria from stromal to malignant cells, to interfere with mitochondrial biogenesis, to directly inhibit respiratory chain complexes, or to disrupt mitochondrial function in other ways. For the experimental treatment of cancers, OXPHOS inhibitors can be advantageously combined with tyrosine kinase inhibitors, as well as with other strategies to inhibit glycolysis, thereby causing a lethal energy crisis. Unfortunately, most of the preclinical data arguing in favor of OXPHOS inhibition have been obtained in xenograft models, in which human cancer cells are implanted in immunodeficient mice. Future studies on OXPHOS inhibitors should elaborate optimal treatment schedules and combination regimens that stimulate—or at least are compatible with—anticancer immune responses for long‐term tumor control.

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Section: Strategies For Oxphos Inhibitionmentioning

confidence: 99%

Section: Strategies For Oxphos Inhibitionmentioning

confidence: 99%

Oxidative phosphorylation as a potential therapeutic target for cancer therapy

Sica

Pedro

Stoll

et al. 2019

Intl Journal of Cancer

148

114

View full text Add to dashboard Cite

show abstract

“…Hence, appropriate clinical usage for the repurposing of these drugs would be in the context of pretreating to chemosensitize tumor cells to enhance their pro‐oxidative stress, which greatly improves preclinical and clinical responses to chemotherapy at all stages of cancer progression (initial to metastatic stages). The past decade has witnessed the emergence of mitocans (mitochondrially targeted anticancer drugs) as a novel paradigm for cancer therapy and one that has the added advantage of targeting the CSCs (for review, see Skoda et al). The accumulating evidence from the preclinical and clinical studies supports the application of such drugs during the primary treatment phase, as well as during longer term adjuvant therapy, used in combination with the more common chemotherapies (such as anthracyclines) to improve outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, a more selective and specific targeting approach is needed that preferentially distinguishes cancer from normal cells. By changing the traditional approach of only looking for differences in the transcriptome or the proteome and instead searching for significant changes in function, such a target may be the reprogrammed redox metabolism found inside advanced stage cancer cells, particularly metastatic cells and cancer stem cells (CSCs; reviewed in Ralph et al and Skoda et al) (Table ).…”

Section: Introductionmentioning

confidence: 99%

Repurposing drugs as pro‐oxidant redox modifiers to eliminate cancer stem cells and improve the treatment of advanced stage cancers

Ralph

Nozuhur

ALHulais

et al. 2019

Medicinal Research Reviews

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Over the last decade, three major advances have contributed in improving the response rates against cancer including, immunotherapy; greater understanding of the molecular, biochemical, and cellular mechanisms in carcinogenesis thereby providing drug targets; and identification of reliable biomarkers for early detection to facilitate the earlier stage treatment of disease. However, no single universal cancer cure has yet been found, although combinations from the above areas have steadily improved survival outcomes. Hence, chemotherapy remains a key component in the oncologist's arsenal for cancer therapy, despite frequent development of drug resistance and more aggressive cancers with onset of advanced stage metastases. The focus here is to explore the repurposing of old drugs that cause pro‐oxidative overload to overcome onset of resistance to chemotherapy and enhance chemotherapeutic responses, particularly against metastatic cancer. Excellent examples of US Food and Drug Administration approved drugs suitable for repurposing are the potent and specific thioreductase inhibitor auranofin and the nonsteroidal anti‐inflammatory drug, celecoxib. Recently, both drugs were shown to selectively target and kill metastatic cancer cells and cancer stem cells (CSCs), predominantly by promoting excessive mitochondrial reactive oxygen species. Thus, targeting intracellular redox systems of advanced stage metastatic cancer cells and CSCs can promote an overload of pro‐oxidative stress to activate the intrinsic pathway for programmed cell death. It is envisaged that more clinical studies will incorporate longer term use of repurposed drugs, such as auranofin or celecoxib, to target redox systems in cancer cells as part of common practice postcancer diagnosis, providing enhanced chemotherapeutic responses and increased cancer survival.

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“…We propose to enhance the therapeutic development by identifying and repurposing the existing FDA‐approved medications with mitochondria‐targeted properties. On the other hand, dietary and herbal supplements and other new approaches should also be explored for their potential to modulate or restore mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

Mitochondria in the biology, pathogenesis, and treatment of hepatitis virus infections

Zhang

et al. 2019

Reviews in Medical Virology

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Summary Hepatitis virus infections affect a large proportion of the global population. The host responds rapidly to viral infection by orchestrating a variety of cellular machineries, in particular, the mitochondrial compartment. Mitochondria actively regulate viral infections through modulation of the cellular innate immunity and reprogramming of metabolism. In turn, hepatitis viruses are able to modulate the morphodynamics and functions of mitochondria, but the mode of actions are distinct with respect to different types of hepatitis viruses. The resulting mutual interactions between viruses and mitochondria partially explain the clinical presentation of viral hepatitis, influence the response to antiviral treatment, and offer rational avenues for novel therapy. In this review, we aim to consider in depth the multifaceted interactions of mitochondria with hepatitis virus infections and emphasize the implications for understanding pathogenesis and advancing therapeutic development.

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Pharmacological targeting of mitochondria in cancer stem cells: An ancient organelle at the crossroad of novel anti-cancer therapies

Cited by 59 publications

References 244 publications

Oxidative phosphorylation as a potential therapeutic target for cancer therapy

Oxidative phosphorylation as a potential therapeutic target for cancer therapy

Repurposing drugs as pro‐oxidant redox modifiers to eliminate cancer stem cells and improve the treatment of advanced stage cancers

Mitochondria in the biology, pathogenesis, and treatment of hepatitis virus infections

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