Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients

Schwarzenbach, Heidi; Gahan, P. B.

doi:10.20517/cdr.2019.010

Cited by 16 publications

(15 citation statements)

References 180 publications

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“…Epigenetic gene silencing is increasingly being recognized as contributing to the development of cisplatin resistance. The treatment with demethylating agents, such as 5-aza-2′-deoxycytidine, resensitizes patients to platinum therapy, which is evidence of the critical importance of DNA methylation in drug resistance [ 250 , 251 ]. MAL transcript levels are higher in cis-platinum-resistant ovarian cell lines.…”

Section: Mal In Cancermentioning

confidence: 99%

The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

Rubio-Ramos

Labat-de-Hoz

Correas

et al. 2021

Cells

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The MAL gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell. Since its original description more than thirty years ago, a large body of evidence has accumulated supporting a role of MAL in specialized membranes in all the cell types in which it is expressed. Here, we review the structure, expression and biochemical characteristics of MAL, and discuss the association of MAL with raft membranes and the function of MAL in polarized epithelial cells, T lymphocytes, and myelin-forming cells. The evidence that MAL is a putative receptor of the epsilon toxin of Clostridium perfringens, the expression of MAL in lymphomas, the hypermethylation of the MAL gene and subsequent loss of MAL expression in carcinomas are also presented. We propose a model of MAL as the organizer of specialized condensed membranes to make them functional, discuss the role of MAL as a tumor suppressor in carcinomas, consider its potential use as a cancer biomarker, and summarize the directions for future research.

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Section: Mal In Cancermentioning

confidence: 99%

The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

Rubio-Ramos

Labat-de-Hoz

Correas

et al. 2021

Cells

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“…Epigenetic modifications lead to cis-or carboplatin-resistant ovarian cancers. Hypermethylation-mediated repression of cell adhesion and tight junction pathways as well as hypomethylation-mediated activation of the cell growth-promoting pathways PI 3 K/Akt and Transforming growth factor β (TGF-β) may contribute to platinum resistance [49]. Besides chromosomal modifications, non-coding RNAs such as miRNAs and long non-coding RNAs (lncRNAs) also play an important role in chemoresistance.…”

Section: Acquired Chemoresistancementioning

confidence: 99%

Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them

Ramos

Sadeghi

Tabatabaeian

2021

IJMS

109

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With nearly 10 million deaths, cancer is the leading cause of mortality worldwide. Along with major key parameters that control cancer treatment management, such as diagnosis, resistance to the classical and new chemotherapeutic reagents continues to be a significant problem. Intrinsic or acquired chemoresistance leads to cancer recurrence in many cases that eventually causes failure in the successful treatment and death of cancer patients. Various determinants, including tumor heterogeneity and tumor microenvironment, could cause chemoresistance through a diverse range of mechanisms. In this review, we summarize the key determinants and the underlying mechanisms by which chemoresistance appears. We then describe which strategies have been implemented and studied to combat such a lethal phenomenon in the management of cancer treatment, with emphasis on the need to improve the early diagnosis of cancer complemented by combination therapy.

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“…Approximately 15~20% of EOCs occur in a familial context with a high penetrant autosomal dominant genetic predisposition. To increase EOC patient survival, application of biomarkers for early diagnosis/detection and risk factor prediction, including genomic/epigenomic variants, copy number aberrations (CNAs), and DNA methylation in EOC surveillance are promising [66,70]. Moreover, due to rapid developments in DNA sequencing technology, various novel germline mutations have also been identified in familial EOC cases and in patients with early-onset EOC.…”

Section: Molecular Markers For Surveillance Of Eocsmentioning

confidence: 99%

The Molecular Landscape Influencing Prognoses of Epithelial Ovarian Cancer

2021

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Epithelial ovarian cancer (EOC) is one of the major increasing lethal malignancies of the gynecological tract, mostly due to delayed diagnosis and chemoresistance, as well as its very heterogeneous genetic makeup. Application of high-throughput molecular technologies, gene expression microarrays, and powerful preclinical models has provided a deeper understanding of the molecular characteristics of EOC. Therefore, molecular markers have become a potent tool in EOC management, including prediction of aggressiveness, prognosis, and recurrence, and identification of novel therapeutic targets. In addition, biomarkers derived from genomic/epigenomic alterations (e.g., gene mutations, copy number aberrations, and DNA methylation) enable targeted treatment of affected signaling pathways in advanced EOC, thereby improving the effectiveness of traditional treatments. This review outlines the molecular landscape and discusses the impacts of biomarkers on the detection, diagnosis, surveillance, and therapeutic targets of EOC. These findings focus on the necessity to translate these potential biomarkers into clinical practice.

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Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients

Cited by 16 publications

References 180 publications

The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them

The Molecular Landscape Influencing Prognoses of Epithelial Ovarian Cancer

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