Cisplatin-Based Chemotherapy Options for Recurrent and/or Metastatic Squamous Cell Cancer of the Head and Neck

Pendleton, Kelsey; Grandis, Jennifer R.

doi:10.4137/cmt.s10409

Cited by 53 publications

(54 citation statements)

References 82 publications

(90 reference statements)

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“…Cisplatin is one of the most common antitumor drugs in the treatment of the advanced cancers, including head and neck cancer, but its efficacy is limited due to both intrinsic and acquired resistance, as well as toxicity [49–51]. We tested the sensitivity of a set of head and neck cell lines to cisplatin treatment by MTT assay and noted that the O28 cell line is relatively resistant to cisplatin with an IC50 value at 18 μM.…”

Section: Resultsmentioning

confidence: 99%

A positive feedback loop involving EGFR/Akt/mTORC1 and IKK/NF-κB regulates head and neck squamous cell carcinoma proliferation

Yang

Passaniti

et al. 2016

Oncotarget

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The overexpression or mutation of epidermal growth factor receptor (EGFR) has been associated with a number of cancers, including head and neck squamous cell carcinoma (HNSCC). Increasing evidence indicates that both the phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of Rapamycin (mTOR) and the nuclear factor-kappa B (NF-κB) are constitutively active and contribute to aggressive HNSCC downstream of EGFR. However, whether these two oncogenic signaling pathways exhibit molecular and functional crosstalk in HNSCC is unclear. Our results now reveal that mTORC1, not mTORC2, contributes to NF-κB activation downstream of EGFR/PI3K/Akt signaling. Mechanistically, mTORC1 enhances the inhibitor of nuclear factor kappa-B kinase (IKK) activity to accelerate NF-κB signaling. Concomitantly, activated NF-κB/IKK up-regulates EGFR expression through positive feedback regulation. Blockage of NF-κB/IKK activity by the novel IKKβ specific inhibitor, CmpdA, leads to significant inhibition of cell proliferation and induction of apoptosis. CmpdA also sensitizes intrinsic cisplatin-resistant HNSCC cells to cisplatin treatment. Our findings reveal a new mechanism by which EGFR/PI3K/Akt/mTOR signaling promotes head and neck cancer progression and underscores the need for developing a therapeutic strategy for targeting IKK/NF-κB either as a single agent or in combination with cisplatin in head and neck cancer.

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Section: Resultsmentioning

confidence: 99%

A positive feedback loop involving EGFR/Akt/mTORC1 and IKK/NF-κB regulates head and neck squamous cell carcinoma proliferation

Yang

Passaniti

et al. 2016

Oncotarget

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“…Cisplatin is the major chemotherapy for SCC but severe side effects and drug resistance are increasing in oral cancer after the cisplatin treatment (Yamano et al, 2010;Pendleton and Grandis, 2013). Thus, several studies are focused to identify the novel and effective therapeutic agents for treating SCC that is necessary (Wang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling

et al. 2016

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Epigallocatechin gallate (EGCG) is a green tea polyphenol that presents anticancer activities in multiple cancer cells, but no available report was addressed for the underling molecular mechanism of cytotoxic impacts on drug-resistant oral squamous cell carcinoma cells. In the present study, the inhibitory effects of EGCG were experienced on cisplatin-resistant oral cancer CAR cells. EGCG inhibited cell viability in a time- and concentration-dependent manner by a sulforhodamine B (SRB) assay. EGCG induced CAR cell apoptosis and autophagy by 4',6-diamidino-2-phenylindole (DAPI) dye, acridine orange (AO) staining and green fluorescent protein (GFP)-tagged LC3B assay, respectively. EGCG also significantly enhanced caspase-9 and caspase-3 activities by caspase activity assay. EGCG markedly increased the protein levels of Bax, cleaved caspase-9, cleaved caspase-3, Atg5, Atg7, Atg12, Beclin-1, and LC3B-II, as well as significantly decreased the expression of Bcl-2, phosphorylated AKT (Ser473) and phosphorylation of STAT3 on Tyr705 by western blotting in CAR cells. Importantly, the protein and gene expression of multidrug resistance 1 (MDR1) were dose-dependently inhibited by EGCG. Overall, downregulation of MDR1 levels and alterations of AKT/STAT3 signaling contributed to EGCG-induced apoptosis and autophagy in CAR cells. Based on these results, EGCG has the potential for therapeutic effect on oral cancer and may be useful for long-term oral cancer prevention in the future. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 845-855, 2017.

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“…Cisplatin are employed for the treatment of a variety of tumors, including testicular (Juliachs et al, 2013), ovarian (Mir et al, 2013), head and neck (Pendleton et al, 2013), colorectal (Germani et al, 2013), bladder (Sternberg et al, 2013) and lung cancers (Shin et al, 2013), as a single agent or in combination with other anticancer agents. The prominent mechanism that cisplatin exerts for anticancer effects involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of mitochondrial apoptosis (Galluzzi et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-100 Resensitizes Resistant Chondrosarcoma Cells to Cisplatin through Direct Targeting of mTOR

Zhu

Wang²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Chondrosarcomas are malignant cartilage-forming tumors of bone which exhibit resistance to both chemotherapy and radiation treatment. miRNAs have been well demonstrated to regulate gene expression and play essential roles in a variety of biological processes, including proliferation, differentiation, migration, cell cycling and apoptosis. In this study, we obtained evidence that miR-100 acts as a tumor suppressor in human chondrosarcomas. Interestingly, cisplatin resistant chondrosarcoma cells exhibit decreased expression of miR-100 compared with parental cells. In addition, we identified mTOR as a direct target of miR-100. Overexpression of miR-100 complementary pairs to the 3' untranslated region (UTR) of mTOR, resulted in sensitization of cisplatin resistant cells to cisplatin. Moreover, recovery of the mTOR pathway by overexpression of S6K desensitized the chondrosarcoma cells to cisplatin, suggesting the miR-100-mediated sensitization to cisplatin dependent on inhibition of mTOR. In summary, the present studies highlight miR-100 as a tumor suppressor in chondrosarcoma contributing to anti-chemoresistance. Overexpression of miR-100 might be exploited as a therapeutic strategy along with cisplatin-based combined chemotherapy for the treatment of clinical chondrosarcoma patients.

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Cisplatin-Based Chemotherapy Options for Recurrent and/or Metastatic Squamous Cell Cancer of the Head and Neck

Cited by 53 publications

References 82 publications

A positive feedback loop involving EGFR/Akt/mTORC1 and IKK/NF-κB regulates head and neck squamous cell carcinoma proliferation

A positive feedback loop involving EGFR/Akt/mTORC1 and IKK/NF-κB regulates head and neck squamous cell carcinoma proliferation

Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling

MicroRNA-100 Resensitizes Resistant Chondrosarcoma Cells to Cisplatin through Direct Targeting of mTOR

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