ABCC1 (ATP Binding Cassette Subfamily C Member 1)

Binding of the protein near the inner membrane interface is found to strongly inhibit the function of the efflux pump and sensitize Dox-resistant cancer cells to the drug, reducing its IC50 value by ∼25%. These results illustrate a new strategy for inhibiting intracellular proteins and identifying potential functional linear motifs in unstructured regions of proteins, benefiting from the facile preparation of the MINPs for different peptide sequences, their highly specific binding abilities, and their ability to enter cells.

Functional enrichment analysis further linked the ABCC1-centred phospho-network to carcinogenesis, cell-cycle regulation, and drug resistance pathways, highlighting its systems-level role in cancer biology. From a translational perspective, our findings identify phosphosites within the ABCC1 linker domain as actionable regulatory nodes that may be exploited to modulate transporter function, offering potential strategies to overcome chemoresistance.

β-Estradiol mitigates oxidative stress, induces apoptosis, and suppresses pro-survival, metastatic, and chemoresistant pathways-contrasting testosterone's minimal effects. These findings align with HCC's male predominance and highlight the hormone-modulated strategies' potential for future therapeutic exploration.

Finally, co-treatment with 1l restored sensitivity of ABCG2-overexpressing cells to the anticancer drug SN38, effectively reversing the MDR phenotype. Collectively, these results identify N-methylpyrazole derivatives as promising selective inhibitors of ABCG2.

All the pyrrolobenzodiazepines tested - SJG136, SGD-1882, SG2057, and SG3199 - were substrates of P-gp, ABCG2, and MRP1. The modified anthracyclines nemorubicin and its metabolite PNU-159682 were poorly transported by both ABCB1 and ABCG2 and displayed nanomolar to picomolar toxicity. Further, we found that the efficacy of the FDA-approved ADC mirvetuximab soravtansine, with DM4 as the toxic payload, was decreased in cell lines expressing P-gp... Several commonly used ADC payloads can be transported by ABC transporters, potentially leading to transporter-mediated drug resistance in patients. Future ADCs should be developed using payloads that are not ABC transporter substrates.

Therefore, it might be indicated that BT improved Dox retention and increased the Dox responsiveness in A549 cells. BT-mediated selective suppression of the NRF2, re-stabilized the KEAP-1-independent NRF2 regulators and made the non-responsive A549 cells partially sensitive to Dox.

We concluded for the first time that the combination of SOR and ASH-AE generates antagonistic antitumor effect in HepG2 cells. Moreover, ASH-AE can inhibit proliferation of HepG2 cells and mitigate sorafenib-induced resistance-associated markers in HepG2 cells by targeting CD90+ cells via Hedgehog pathway modulation.

At the same time, we point out bottlenecks, such as low bioavailability, insufficient in vivo evidence, and unclear structure-activity relationship and put forward a proposal to address these bottlenecks. At the same time, the bottlenecks of low bioavailability, insufficient vivo evidence and unclear structure-activity relationship have been pointed out, and future research directions such as nano-delivery, structural optimization and combination strategies have been proposed to provide theoretical foundations and potential practical pathways for the clinical translation research of terpenoid compounds, whose clinical application still requires further in vivo validation and translational research support.

These findings indicate that agmatine exerts antiproliferative, anti-migratory, anti-invasive, and pro-apoptotic effects in Caco-2 colon cancer cells, potentially through the modulation of apoptosis- and oxidative stress-related pathways. The lack of significant impacts on ABC transporter gene expression suggests that agmatine may be a promising candidate molecule for further translational studies in colorectal cancer.

In HER2 mutant NSCLC patients, loss of HER2 is not a universal mechanism of T-DXd resistance. Collectively, these data highlight multiple mechanisms of resistance to T-DXd that do not result in loss of HER2 TKI responsiveness.

In patients with R/R AML, the CACAG-VEN regimen resulted in significant clinical benefits, with a high CRc rate and encouraging survival, as well as being well tolerated. https://www.chictr.org.cn/, identifier, ChiCTR2200065634.

A prognostic signature based on the expression levels of three resistome-associated genes has been defined and can serve as a helpful complementary tool in clinical settings to categorize HCC patients.