ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer

Palshof, Jesper Andreas; Cederbye, Camilla Natasha; Høgdall, Estrid; Poulsen, Tim Svenstrup; Linnemann, Dorte; Nygaard, Sune Boris; Stenvang, Jan; Christensen, Ib Jarle; Jensen, Benny Vittrup; Pfeiffer, Per; Brünner, Nils; Yilmaz, Mette Karen; Viuff, Birgitte; Nielsen, Dorte

doi:10.3390/ijms21145027

Cited by 8 publications

(6 citation statements)

References 33 publications

(49 reference statements)

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“…Moreover, the chemotherapeutics from nonsubstrates of ABCB1 may increase its mRNA expression [ 179 ]. Complementary to this, some tumor cells may also express other efflux transporters responsible for drug resistance, such as ABCG2 (breast cancer resistance protein, BCRP) [ 180 ] or ABCC1 (multidrug-resistance-associated protein 1, MRP1) [ 181 ]. That is why looking for new drugs with the potential to overcome drug efflux is an intensive challenge for experts from various fields.…”

Section: The Potential Of Agnps In Nano-oncologymentioning

confidence: 99%

The Role of Silver Nanoparticles in the Diagnosis and Treatment of Cancer: Are There Any Perspectives for the Future?

Takáč

Michalková

Čižmáriková

et al. 2023

Life

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Cancer is a fatal disease with a complex pathophysiology. Lack of specificity and cytotoxicity, as well as the multidrug resistance of traditional cancer chemotherapy, are the most common limitations that often cause treatment failure. Thus, in recent years, significant efforts have concentrated on the development of a modernistic field called nano-oncology, which provides the possibility of using nanoparticles (NPs) with the aim to detect, target, and treat cancer diseases. In comparison with conventional anticancer strategies, NPs provide a targeted approach, preventing undesirable side effects. What is more, nanoparticle-based drug delivery systems have shown good pharmacokinetics and precise targeting, as well as reduced multidrug resistance. It has been documented that, in cancer cells, NPs promote reactive oxygen species (ROS) production, induce cell cycle arrest and apoptosis, activate ER (endoplasmic reticulum) stress, modulate various signaling pathways, etc. Furthermore, their ability to inhibit tumor growth in vivo has also been documented. In this paper, we have reviewed the role of silver NPs (AgNPs) in cancer nanomedicine, discussing numerous mechanisms by which they render anticancer properties under both in vitro and in vivo conditions, as well as their potential in the diagnosis of cancer.

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Section: The Potential Of Agnps In Nano-oncologymentioning

confidence: 99%

The Role of Silver Nanoparticles in the Diagnosis and Treatment of Cancer: Are There Any Perspectives for the Future?

Takáč

Michalková

Čižmáriková

et al. 2023

Life

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“…Both localizations were also detected by Hu J et al [ 24 ] in right-sided colorectal cancer tissues. Palshof et al [ 58 ] reported recently that in addition to the cytoplasm, ABCG2 expression was also present in both the apical/luminal and basolateral membranes of the colorectal cancer cells. It could be speculated that subcellular localization of the ABCG2 can be associated with specific function or loss of function of the transporter during colorectal carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Some negative findings were published. No association has been found between ABCG2 expression and clinicopathological parameters [ 56 ], or between the expression of ABCG2 protein (basolateral, apical or cytoplasmatic) and age, sex, WHO performance status, location of the primary tumour, number of metastatic sites or liver or lung metastases in colorectal cancer [ 58 ]. Gupta et al [ 26 ] indicated no significant correlation between ABCG2 mRNA level and age, sex, population type, grade, stage or localization, and Halavata et al [ 49 ] reported no connection between ABCG2 expression with the grade, primary localization, T, N, M, age at diagnosis or sex.…”

Section: Discussionmentioning

confidence: 99%

ABCG2 Gene and ABCG2 Protein Expression in Colorectal Cancer—In Silico and Wet Analysis

Sałagacka-Kubiak,

Zawada,

Saed

et al. 2023

IJMS

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ABCG2 (ATP-binding cassette superfamily G member 2) is a cell membrane pump encoded by the ABCG2 gene. ABCG2 can protect cells against compounds initiating and/or intensifying neoplasia and is considered a marker of stem cells responsible for cancer growth, drug resistance and recurrence. Expression of the ABCG2 gene or its protein has been shown to be a negative prognostic factor in various malignancies. However, its prognostic significance in colorectal cancer remains unclear. Using publicly available data, ABCG2 was shown to be underexpressed in colon and rectum adenocarcinomas, with lower expression compared to both the adjacent nonmalignant lung tissues and non-tumour lung tissues of healthy individuals. This downregulation could result from the methylation level of some sites of the ABCG2 gene. This was connected with microsatellite instability, weight and age among patients with colon adenocarcinoma, and with tumour localization, population type and age of patients for rectum adenocarcinoma. No association was found between ABCG2 expression level and survival of colorectal cancer patients. In wet analysis of colorectal cancer samples, neither ABCG2 gene expression, analysed by RT-PCR, nor ABCG2 protein level, assessed by immunohistochemistry, was associated with any clinicopathological factors or overall survival. An ABCG2-centered protein–protein interaction network build by STRING showed proteins were found to be involved in leukotriene, organic anion and xenobiotic transport, endodermal cell fate specification, and histone methylation and ubiquitination. Hence, ABCG2 underexpression could be an indicator of the activity of certain signalling pathways or protein interactors essential for colorectal carcinogenesis.

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“… Wang et al (2021) reported that ABCG2 rs1871744 and rs4148157 genotype were significantly associated with the poor response in cancer patients receiving platinum-based chemotherapy. Palshof et al (2020) found that colorectal cancer patients with low ABCG2 expression level had a higher chance of obtaining objective response when receiving irinotecan-based treatment. Hence, identifying anticancer drugs that are ABCG2 substrates can be beneficial to the development of clinical treatment strategy and to monitor the occurrence of drug resistance.…”

Section: Introductionmentioning

confidence: 96%

Overexpression of ABCG2 Confers Resistance to MLN7243, a Ubiquitin-Activating Enzyme (UAE) Inhibitor

Yang

Wang

et al. 2021

Front. Cell Dev. Biol.

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Overexpression of ATP-binding cassette transporter superfamily G member 2 (ABCG2), is known as a major mechanism mediating multidrug resistance (MDR) in cancer cells. MLN7243 is a small-molecule ubiquitin activating enzyme inhibitor currently under clinical investigation. The aim of the current study is to determine if MLN7243 is a substrate of MDR-related ABCG2 transporter. Our results showed that cancer cells overexpressing ABCG2 transporter were resistant to MLN7243 compared to the parental cells, while knockout of ABCG2 gene or pharmacological inhibition of ABCG2 efflux function completely reversed the drug resistance. Unexpectedly, the endogenous low expression of ABCG2 is sufficient to confer cancer cells resistance to MLN7243. The ABCG2 ATPase assay and HPLC assay suggested that MLN7243 can significantly stimulate ABCG2 ATPase activity and be pumped out from ABCG2-overexpressing cells by ABCG2. The docking analysis also implied that MLN7243 binds to ABCG2 drug-binding pocket with optimal binding affinity. However, MLN7243 did not competitively inhibit the efflux of other ABCG2 substrate drugs, indicating it may not serve as an MDR reversal agent. In conclusion, our study provides direct in vitro evidence to show that MLN7243 is a potent ABCG2 substrate. If our results can be translated to humans, it suggests that combining MLN7243 with ABCG2 inhibitors may enhance the anticancer efficacy for patients with high tumor ABCG2 level.

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ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer

Cited by 8 publications

References 33 publications

The Role of Silver Nanoparticles in the Diagnosis and Treatment of Cancer: Are There Any Perspectives for the Future?

The Role of Silver Nanoparticles in the Diagnosis and Treatment of Cancer: Are There Any Perspectives for the Future?

ABCG2 Gene and ABCG2 Protein Expression in Colorectal Cancer—In Silico and Wet Analysis

Overexpression of ABCG2 Confers Resistance to MLN7243, a Ubiquitin-Activating Enzyme (UAE) Inhibitor

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