ABCC10 (ATP Binding Cassette Subfamily C Member 10)

SIGNIFICANCE STATEMENT: This study provides evidence that BRG1 inhibition with PFI3 and degradation of SMARCA4 mRNA substantially declines lysosomal drug sequestration and potentiate drug toxicity. Therefore, BRG1 targeting can be considered as candidate for combinatorial anticancer therapy with some standard chemotherapy drugs.

To assess clinical relevance, blood samples from 109 gefitinib/erlotinib- and 54 osimertinib-treated patients were analyzed for these SNPs. These findings suggest that ABC transporter SNPs could be valuable biomarkers for personalized medicine in NSCLC. These findings suggest that ABC transporter SNPs may serve as valuable biomarkers for predicting EGFR-TKI efficacy in NSCLC patients with EGFR mutations, which will contribute to personalized medicine.

Analysis of The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases confirmed a likely role of HIF1A-BRG1-p300 overexpression in the taxanes resistance of cancer patients and the possible biomarker function of this protein in cancer responses to chemotherapy. Therefore, the complex comprising BRG1-EP300-HIF1A can be considered for further clinical investigation and planning for patient therapy.

In vivo, a combination of RT and nilotinib, a potential ABCC10 inhibitor, synergistically inhibited tumor growth. In summary, we identified ABCC10 as a novel exporter of cGAMP in RTR. Our results highlight its potential role as a biomarker for predicting RT response and as a therapeutic target for overcoming RTR.

The overexpression of ABCC1 and ABCC10 in tumour tissues, particularly in poor responders, suggests their potential role in mediating docetaxel resistance. These findings highlight ABCC1 and ABCC10 as potential predictive biomarkers for docetaxel treatment response in PCa, warranting further investigation in prospective clinical studies.

Multidrug resistance (MDR) in cancer is often associated with overexpression of ABC transporter proteins, which can lead to failure of cancer treatments. Additionally, the relationship of miRNAs with ABC transporter proteins constitutes an important research area to understand the mechanisms of drug resistance and develop new treatment strategies.

Furthermore, OAShi tumors such as MC38 naturally produced 2-5A in vivo, which was secreted via ABCC10 to activate host-not tumor-RNase L-mediated antitumor response. Therefore, 2-5A is an immunotransmitter that mediates short-range communication between cells in infection and cancer.

Thus, not only expression but also chromosomal aberrations were found to be associated with patient survival. These findings could be a potential marker of metastatic-free survival.

Furthermore, molecular blind docking experiments and advanced binding site analyses revealed, for the first time, conserved binding motifs across monocarboxylate transporters (MCTs), organic anion transporting polypeptides (OATPs), organic cation transporters (OCTs), and ABC transporters, characterized by specific and recurring residues of tyrosine, phenylalanine, serine, and threonine. These findings highlight not only the potential of polypharmacology in drug discovery but also provide insights into the structural underpinnings of ligand binding across membrane transporters.

We further discussed that the most commonly used drugs in standard regimens for mainly breast cancer, lung cancer, and acute lymphoblastic leukemia could be subject to MDR mediated by ABC transporters. Collectively, these insights will aid in conducting new studies aimed at a deeper understanding of the clinical MDR mediated by ABC proteins and in designing more effective pharmacological treatments to enhance the objective response rate in cancer patients.

In this study, we present a novel fertility protection method using MSC-derived exosomes. We conclude that MSC-derived exosomes are a promising simple treatment option for fertility protection in reproductive-age patients receiving gonadotoxic chemotherapy.

The transport substrates of ABCC10/MRP7 include antineoplastic drugs such as taxanes, vinca alkaloids, and epothilone B, as well as endobiotics such as leukotriene C4 (LTC4) and estradiol 17 β-D-glucuronide. A variety of ABCC10/MRP7 inhibitors, including cepharanthine, imatinib, erlotinib, tariquidar, and sildenafil, can reverse ABCC10/MRP7-mediated MDR. Additionally, the presence or absence of ABCC10/MRP7 is also closely related to renal tubular dysfunction, obesity, and other diseases. In this review, we discuss: 1) Structure and functions of ABCC10/MRP7; 2) Known substrates and inhibitors of ABCC10/MRP7 and their potential therapeutic applications in cancer; and 3) Role of ABCC10/MRP7 in non-cancerous diseases.