Copyright ©The Author(s) 2017.
World J Stem Cells. Aug 26, 2017; 9(8): 118-126
Published online Aug 26, 2017. doi: 10.4252/wjsc.v9.i8.118
Table 1 Cancer stem cells and epithelial-mesenchymal transition targeted therapy
Cancer typeBiological mechanism(s) of resistanceTargeted therapy andtherapeutic functionsClinical trial if anyRef.
CRPCSkp2 regulates CRPC through Twist-mediated oncogenic functions including EMT and CSCs acquisitionGenetic or pharmacological inactivation of Skp2 re-sensitize CRPC cells toward chemotherapies such as paclitaxel or doxorubicinNone[40]
Lung cancerHigh levels of circulating IGF1 lead to EMT induction and CSC maintenanceUse of IGF1R inhibitors sensitize cancer cells to killing effects of carboplatin, paclitaxel, docetaxel, and vinorelbinePhase I trial[41]
Ovarian cancer, advanced solid tumorsFAK linked with WNT, TGF-beta, Integrin and Hedgehog pathways, mediate cell invasion and metastasisAnti-sense FAK oligonucleotides, adenoviral dominant-negative FAK-CD, FAK siRNA, pharmacological inhibitors affect tumor cells and microenvironmentPhase I trial[42,43]
Invasive ductal breast cancerElevated expression of ABC drug transporters, induction of Wnt/β-catenin, Hedgehog, Notch and PI3K/Akt/mTOR signaling pathways, and acquisition of EMTSalinomycin promotes differentiation of CSCs, epithelial reprogramming of cells that had undergone EMTClinical pilot studies[44]
Human lung epithelial cellsActivation of TGF-β/Smad signaling pathway, induction of EMT and therapy resistanceUse of drug, lerdelimumab, which acts as monoclonal antibody to TGF-β1Preclinical[45]
Renal cell carcinoma, malignant melanomaActivation of TGF-β/Smad signaling pathway, induction of EMT and therapy resistanceUse of drug, GC1008, which acts as monoclonal antibody to TGF-β1Phase I trial[46]
Glioblastoma/anaplastic astrocytomaActivation of TGF-β/Smad signaling pathway, induction of EMT and therapy resistanceAntisense oligodeoxynucleotide specific for the mRNA of human TGF-β2Phase I/II trial[47]
Renal cell carcinoma, advanced cancersInflammatory cytokines including TNF-α and IL6 promote EMT and tumor invasionInfliximab, a TNF-α monoclonal blocking antibody suppresses the levels of IL6 and CCL2Phase II trial[48,49]
Metastatic gastric adenocarcinoma, recurrent and metastatic head and neck squamous cell carcinomaActivation of NF-κB and TNF-α signalingBortezomib, a proteasome inhibitor suppresses NFκB activationPhase II trial[50,51]
Advanced solid tumors; advanced lung cancerIncreased expression of HIF-1αDrug, PX-478 inhibits HIF1α expression Topotecan along with conventional chemotherapies such as cisplatin or bevacizumab inhibit HIF-1α expressionPhase I trial Phase I/II trial[52,53]