Targeting histone deacetylase SIRT1 selectively eradicates EGFR TKI-resistant cancer stem cells via regulation of mitochondrial oxidative phosphorylation in lung adenocarcinoma.
Alternatively, through drug repositioning of approved drugs, we discovered that the FMS-like tyrosine kinase-3 (FLT3) inhibitor midostaurin blocks the drug transport function of ABCB1 and re-sensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic drugs.
Furthermore, TKI-induced EGFR dimerization is persistent in TKI-resistant cells, and inhibition of palmitoylation by 2-bromopalmitate, or targeted reduction of the kinase-inactivated EGFR by siRNA or by an EGFR-downregulating peptide, are lethal to TKI-resistant cancer cells.
Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells.
Thus, Pgp has become an attractive potential target for treating chemotherapy-resistant cancer, but the outcomes of using chemotherapy in combination with Pgp inhibitors in clinical trials to date have been disappointing.
In the aggregate, newly synthesized MSNP-PEI-DOX/MDR1-siRNA improves cancer chemotherapy effect in terms of treating multidrug-resistant cancer compared to DOX only, clearly demonstrating that MSNP-PEI-DOX/MDR1-siRNA has potential therapeutic application for multidrug-resistant cancer in the future.
The multidrug transporter permeability (P)-glycoprotein is an adenosine triphosphate (ATP)-binding cassette exporter responsible for clinical resistance to chemotherapy.
When treated with pyruvate, both HT29-dx and HMM cells exhibited a re-established accumulation of doxorubicin and a lower survival ability, a decreased activity of multidrug resistance protein 1 (MRP1) and a restored mitochondrial respiratory chain function, improving the effectiveness of the chemotherapeutic agents in these resistant cancer cells.
These data demonstrated that activation of PPARγ mediated by troglitazone enhances human lung cancer cells to TRAIL-induced apoptosis via autophagy flux and also suggest that troglitazone may be a combination therapeutic target with TRAIL protein in TRAIL-resistant cancer cells.
Patients with EGFR-mutant lung cancers treated with EGFR tyrosine kinase inhibitors (TKIs) develop clinical resistance, most commonly with acquisition of EGFR T790M.
P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) are ATP binding cassette (ABC) transporters that are overexpressed in different drug-resistant cancer cell lines.
These data demonstrate that inhibition of Akt/mTOR by glipizide sensitizes TRAIL-induced tumor cell death through activating autophagy flux and also suggest that glipizide may be a combination therapeutic target with TRAIL protein in TRAIL-resistant cancer cells.
Here we show that TRAIL-triggered cytokine secretion from TRAIL-resistant cancer cells is FADD dependent and identify the TRAIL-induced secretome to drive monocyte polarization to myeloid-derived suppressor cells (MDSCs) and M2-like macrophages.
These findings provide important information regarding the sensitization of highly HAL-resistant cells with selective P-gp inhibitors and indicate that elacridar may be used to treat such highly HAL-resistant cancer cells.
In conclusion, combined targeting of MAPK and PI3K/AKT signaling, but not single pathways, may be required to enhance the efficacy of anti-EGFR antibody therapy in patients with RAS-mutated CRC as well as in RAS wild type tumors with clinical resistance.
Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression.
Among the 18 TRAIL-resistant cancer cell lines used, 15 cell lines become sensitive or highly sensitive to ART, and two out of three glioma cell lines exhibit high resistance to ART treatment due to very low levels of procaspase-8.
Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy.