Role of copper transporters in platinum resistance

Kilari, Deepak; Guancial, Elizabeth A.; Kim, Eric S.

doi:10.5306/wjco.v7.i1.106

Cited by 104 publications

(71 citation statements)

References 74 publications

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“…Increased CTR1 expression by the cells results in an increased platinum concentration and decreased resistance to cisplatin . Combination of platinum drugs with bortezomib, a modulator for copper transporter expression, is a current option for platinum‐resistant solid tumors …”

Section: Multiple Drug Resistancementioning

confidence: 99%

Ovarian cancer: Current status and strategies for improving therapeutic outcomes

Pius²,

et al. 2019

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Of all the gynecologic tumors, ovarian cancer (OC) is known to be the deadliest. Advanced‐stages of OC are linked with high morbidity and low survival rates despite the immense amount of research in the field. Shortage of promising screening tools for early‐stage detection is one of the major challenges linked with the poor survival rate for patients with OC. In OC, therapeutic management is used with multidisciplinary approaches that includes debulking surgery, chemotherapy, and (rarely) radiotherapy. Recently, there is an increasing interest in using immunomodulation for treating OC. Relapse rates are high in this malignancy and averages around every 2‐years. Further treatments after the relapse are more intense, increasing the toxicity, resistance to chemotherapy drugs, and financial burden to patients with poor quality‐of‐life. A procedure that has been studied to help reduce the morbidity rate involves pre‐sensitizing cancer cells with standard therapy in order to produce optimal results with minimum dosage. Utilizing such an approach, platinum‐based agents are effective due to their increased response to platinum‐based chemotherapy in relapsed cases. These chemo‐drugs also help address the issue of drug resistance. After conducting an extensive search with available literature and the resources for clinical trials, information is precisely documented on current research, biomarkers, options for treatment and clinical trials. Several schemes for enhancing the therapeutic responses for OC are discussed systematically in this review with an attempt in summarizing the recent developments in this exciting field of translational/clinical research.

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Section: Multiple Drug Resistancementioning

confidence: 99%

Ovarian cancer: Current status and strategies for improving therapeutic outcomes

Pius²,

et al. 2019

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“…Recently reviewed results also strongly suggest more complex mechanisms involved in this cytotoxicity, such as the interaction with mitochondria and with the immunologic tumour environment [4]. Several resistance mechanisms have been proposed to be involved in a decreased clinical response to platinum derivatives, such as modified expression of membrane copper transporters [5], increased inactivation of intracellular platinum derivatives by glutathione [6], defects in the apoptotic machinery [7] or increased repair activity on the DNA adducts [8,9].…”

Section: Introductionmentioning

confidence: 99%

Unexpected Growth-Promoting Effect of Oxaliplatin in Excision Repair Cross-Complementation Group 1 Transfected Human Colon Cancer Cells

et al. 2018

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The nucleotide excision repair protein excision repair cross-complementation group 1 (ERCC1) has been repeatedly shown to be involved in the sensitivity of cancer cells to platinum derivatives. In order to better understand this process, we transfected HCT-116 cells with a plasmid encoding ERCC1 and studied their in vitro and in vivo behaviour. No main differences were observed for sensitivity to platinum drugs, DNA repair capacity and clonogenicity in vitro. However, ERCC1-transfected HCT-116 cells showed paradoxical behaviour in vivo with increased growth in mice treated with oxaliplatin as compared to untreated mice. The Trop2 protein was identified as being potentially involved in the underlying mechanism for these observations, as it was overexpressed in transfected cells. Our results suggest complex regulation of signalling in cancer cells exposed to cancer drugs.

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“…Studies have reported that several transporters have different functions to regulate the net intracellular level of platinum drugs [24, 25]. Evidence has indicated that copper transporters have a crucial role in transporting platinum drugs into cells [8, 26]. The major copper influx transporter hCtr1 has been reported to assist the uptake of CDDP, carboplatin, and oxaliplatin and to regulate their cytotoxicity in yeast and mammalian cells [27, 28].…”

Section: Discussionmentioning

confidence: 99%

Desferal regulates hCtr1 and transferrin receptor expression through Sp1 and exhibits synergistic cytotoxicity with platinum drugs in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo

et al. 2016

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The development of resistance to platinum drugs in cancer cells severely reduces the efficacy of these drugs. Thus, the discovery of novel drugs or combined strategies to overcome drug resistance is imperative. In addition to our previous finding that combined D-penicillamine with platinum drugs exerts synergistic cytotoxicity, we recently identified a novel therapeutic strategy by combining an iron chelating agent desferal with platinum drugs to overcome platinum resistance in an oxaliplatin-resistant human cervical cancer cell line, S3. Further study demonstrated that the level of platinum–DNA adduct formation positively correlated with cell death in combination of desferal with platinums than that of each drug alone in S3 cells. Decrement of human copper transporter 1 (hCtr1) and transferrin receptor 1 (TfR1) expression involved in the development of platinum resistance in S3 cells. Moreover, desferal promoted the expression of hCtr1 through the upregulation of Sp1. The overexpression of Sp1 increased the expression of NF-κB and translocated it into the nucleus to bind to the TfR1 promoter region, which subsequently increased the expression of TfR1. Importantly, the cotreatment of oxaliplatin with desferal significantly potentiated the oxaliplatin-elicited antitumoral effect in the oxaliplatin-resistant xenograft animal model without any toxic effect observed. Taken together, these results demonstrated that the combination of desferal with oxaliplatin can overcome oxaliplatin resistance through the regulation of hCtr1 and TfR1, and may have beneficial effect for treatment of patient with oxaliplatin-refractory tumors.

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Role of copper transporters in platinum resistance

Cited by 104 publications

References 74 publications

Ovarian cancer: Current status and strategies for improving therapeutic outcomes

Ovarian cancer: Current status and strategies for improving therapeutic outcomes

Unexpected Growth-Promoting Effect of Oxaliplatin in Excision Repair Cross-Complementation Group 1 Transfected Human Colon Cancer Cells

Desferal regulates hCtr1 and transferrin receptor expression through Sp1 and exhibits synergistic cytotoxicity with platinum drugs in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo

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