Impact of cancer metabolism on therapy resistance – Clinical implications

Gonçalves, Ana Cristina; Richiardone, Elena; Jorge, Joana; Polónia, Bárbara; Xavier, Cristina P.R.; Riganti, Chiara; Vasconcelos, M. Helena; Corbet, Cyril; Sarmento‐Ribeiro, Ana Bela

doi:10.1016/j.drup.2021.100797

Cited by 65 publications

(25 citation statements)

References 407 publications

(454 reference statements)

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“…The direct involvement of MITF in melanoma proliferation, a highly nutrient-demanding state, strongly suggests that it may also participate in controlling the metabolic landscape by providing both the fuel required for the increased energy consumption of a highly replicative cell, and the metabolic bricks to build new macromolecular structures, such as membrane components and DNA. Similarly, low MITF levels presumably contribute to the establishment of the metabolic profile displayed by slow-cycling cells, as well as the metabolic abnormalities generally associated with therapy-resistance, as recently reviewed by Gonçalves et al, 2021. Given the fact that MITF levels confer phenotypic identity, and that MITF expression is suppressed by environmental and metabolic cues, it is not surprising that melanoma tumors, that are highly phenotypically heterogeneous, comprise different cells expressing variable levels of MITF that dictate their tendency to proliferate or invade (Goodall et al, 2008;Pinner et al, 2009). Since high or low MITF expressing cells very likely display distinctive metabolic features in an MITF-dependent manner, different phenotypic melanoma subsets are likely to respond differently to the same microenvironmental signals.…”

Section: The Role Of Mitf In Metabolic Flexibility and Cell Fate Dete...mentioning

confidence: 93%

Connecting Metabolic Rewiring With Phenotype Switching in Melanoma

Falletta

Goding

Vivas-García

2022

Front. Cell Dev. Biol.

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Melanoma is a complex and aggressive cancer type that contains different cell subpopulations displaying distinct phenotypes within the same tumor. Metabolic reprogramming, a hallmark of cell transformation, is essential for melanoma cells to adopt different phenotypic states necessary for adaptation to changes arising from a dynamic milieu and oncogenic mutations. Increasing evidence demonstrates how melanoma cells can exhibit distinct metabolic profiles depending on their specific phenotype, allowing adaptation to hostile microenvironmental conditions, such as hypoxia or nutrient depletion. For instance, increased glucose consumption and lipid anabolism are associated with proliferation, while a dependency on exogenous fatty acids and an oxidative state are linked to invasion and metastatic dissemination. How these different metabolic dependencies are integrated with specific cell phenotypes is poorly understood and little is known about metabolic changes underpinning melanoma metastasis. Recent evidence suggests that metabolic rewiring engaging transitions to invasion and metastatic progression may be dependent on several factors, such as specific oncogenic programs or lineage-restricted mechanisms controlling cell metabolism, intra-tumor microenvironmental cues and anatomical location of metastasis. In this review we highlight how the main molecular events supporting melanoma metabolic rewiring and phenotype-switching are parallel and interconnected events that dictate tumor progression and metastatic dissemination through interplay with the tumor microenvironment.

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Section: The Role Of Mitf In Metabolic Flexibility and Cell Fate Dete...mentioning

confidence: 93%

Connecting Metabolic Rewiring With Phenotype Switching in Melanoma

Falletta

Goding

Vivas-García

2022

Front. Cell Dev. Biol.

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“…Hypoxic stress has been shown in some studies to increase P-gp expression by interacting with the P-gp promoter region via HIF1. In addition, P-gp-independent MDR has also been discovered in osteosarcoma cells [49][50][51].…”

Section: P-gp Expression and Its Structure And Functionsmentioning

confidence: 99%

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein

Karthika

Sureshkumar

Zehravi

et al. 2022

Life

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P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype in cancer cells. P-gp is a protein that regulates the ATP-dependent efflux of a wide range of anticancer medicines and confers resistance. Due to its wide specificity, several attempts have been made to block the action of P-gp to restore the efficacy of anticancer drugs. The major goal has been to create molecules that either compete with anticancer medicines for transport or function as a direct P-gp inhibitor. Despite significant in vitro success, there are presently no drugs available in the clinic that can “block” P-gp–mediated resistance. Toxicity, unfavourable pharmacological interactions, and a variety of pharmacokinetic difficulties might all be the reason for the failure. On the other hand, P-gp has a significant effect in the body. It protects the vital organs from the entry of foreign bodies and other toxic chemicals. Hence, the inhibitors of P-gp should not hinder its action in the normal cells. To develop an effective inhibitor of P-gp, thorough background knowledge is needed in this field. The main aim of this review article was to set forth the merits and demerits of the action of P-gp on cancer cells as well as on normal cells. The influence of P-gp on cancer drug delivery and the contribution of P-gp to activating drug resistance were also mentioned.

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“…The breast-cancer-resistant protein is usually present on chromosomes such as P-gp and MRP-1. This BRCP has a wide range of substrate specificities, which are usually different from but overlaps with P-gp or MRP-1 [ 53 ]. Due to the functioning and the presence of P-gp and MRP, they are considered the targets for various anticancer efforts.…”

Section: Mdr Modulators and The Mechanisms Of Inhibitorsmentioning

confidence: 99%

Multidrug Resistance in Cancer Cells: Focus on a Possible Strategy Plan to Address Colon Carcinoma Cells

Karthika

Sureshkumar

Zehravi

et al. 2022

Life

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Even though various treatment methods are available for cancer, the death curve is not reducing. The diagnosis of cancer at the fourth stage and drug resistance are the leading reasons for treatment failure and lower survival rates. In this review article, we summarize the possible pitfalls during cancer treatment in general, which mainly include multidrug resistance, and propose a hypothesis for colorectal cancer specifically. We also evaluate multidrug resistance in cancer in general and colorectal cancer in particular and hypothesize a concept based on combination therapy with 5-fluorouracil, curcumin, and lipids for the possible management of colorectal cancer. In addition, a hypothetical approach, combining a synthetic agent and a natural chemotherapeutic agent, to treating colorectal cancer is also discussed. This hypothesis could improve the management of colorectal cancer.

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Impact of cancer metabolism on therapy resistance – Clinical implications

Cited by 65 publications

References 407 publications

Connecting Metabolic Rewiring With Phenotype Switching in Melanoma

Connecting Metabolic Rewiring With Phenotype Switching in Melanoma

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein

Multidrug Resistance in Cancer Cells: Focus on a Possible Strategy Plan to Address Colon Carcinoma Cells

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