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.
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.
The overexpression of adenosine triphosphate binding cassette, sub-family B, member 1 (ABCB1) by multidrug-resistant cancer cells is a serious impediment to chemotherapy.
Based on our hypothesis that this clinical resistance to ondansetron is associated with ABCB1 genetic polymorphisms, we investigated whether ABCB1 gene variations affect the efficacy of ondansetron in chemotherapy-induced nausea and vomiting.
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.
Point mutations within the ABL kinase domain are the most frequent mechanism for reactivation of kinase activity of the BCR-ABL gene and have been associated with clinical resistance to tyrosine kinase (TK) inhibitors in patients with CML, conferring a poor prognosis.
Despite the remarkable responses of most patients, a small but significant fraction of patients develops clinical resistance to the TKIs, some of which is attributed to the BCR-ABL kinase domain mutations affecting TKI binding and activity.
Patients with EGFR-mutant lung cancers treated with EGFR tyrosine kinase inhibitors (TKIs) develop clinical resistance, most commonly with acquisition of EGFR T790M.
Besides an enhanced selectivity, these TRAIL-DR4 agonists show superior affinity to DR4, and a high apoptosis-inducing activity against several TRAIL-sensitive and -resistant cancer cell lines in vitro.
The first BCR-ABL inhibitor to come into use in clinical practice, imatinib mesylate, is now the first-choice treatment for all newly diagnosed CML patients, but the initial striking efficacy of this drug has been overshadowed by the development of clinical resistance.
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.
Together, these findings indicate that Pgp plays a role in clinical resistance to gemtuzumab ozogamicin and suggest that treatment trials combining gemtuzumab ozogamicin with MDR reversal agents are warranted.(Blood.2001;98:988-994)
In our present study, we found that carnitine, a metabolite that transfers long-chain fatty acids into mitochondria for beta-oxidation and modulates protein kinase C activity, sensitizes TRAIL-resistant cancer cells to TRAIL.
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.