Molecular Mechanisms of Chemotherapy Resistance in Head and Neck Cancers

Kanno, Yuzuka; Chen, Chang Yu; Lee, Hsin Lun; Chiou, Jeng Fong; Chen, Yin‐Ju

doi:10.3389/fonc.2021.640392

Cited by 41 publications

(55 citation statements)

References 121 publications

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“…Cisplatin’s antitumor activity begins with cellular uptake through copper [ 11 ], anion [ 12 , 13 , 14 ], and cation transporters [ 15 , 16 , 17 , 18 ]. It is subsequently aquated, allowing it to bind to the guanine N 7 position on DNA [ 19 ]. By doing so, cisplatin generates DNA adducts in a highly conserved manner.…”

Section: Cisplatin Mechanism Of Action In Cancer Control and Toxicitymentioning

confidence: 99%

“…ERCC1 is one of the key regulatory proteins within the NER pathway that plays a significant role in the repair of DNA adducts and intrastrand crosslinks (ICLs) generated by cisplatin [ 79 ]. ERCC1 overexpression is found in many different types of cisplatin-resistant cancers, such as HNSCC, bladder, and lung cancers [ 19 , 80 , 81 ]. This makes ERCC1 an important predictive marker for cisplatin treatment.…”

Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

“…Multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), and β-catenin are proteins involved in drug efflux, a mechanism of resistance that maintains cytosolic concentrations of chemotherapy agents below therapeutic levels. MDR1 and MRP1 are ATP-binding cassette proteins that actively pump drug out of the cell and are regulated by β-catenin [ 19 ]. A study found that patients with HNSCC with high expression of MDR1 and MRP1 had significantly lower OS and worse response to cisplatin treatment [ 84 ].…”

Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

“…A study found that patients with HNSCC with high expression of MDR1 and MRP1 had significantly lower OS and worse response to cisplatin treatment [ 84 ]. A knockdown study of β-catenin demonstrated enhanced cisplatin sensitivity, illustrating a relationship between drug transporters, their regulatory signaling pathways, and cisplatin resistance and sensitivity [ 19 , 85 ].…”

Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

“…This correlated to increased cisplatin resistance and poor clinical outcome [ 87 ]. Elevated apollon protein and mRNA expression was also found in HNSCC patients who had lower OS and cisplatin resistance [ 19 , 88 ]. It was also shown that knockdown of livin enhances the apoptotic response in HNSCC cells following cisplatin treatment [ 89 ].…”

Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

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Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

Kiss

Xia

Acklin

2021

IJMS

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Platinum-based chemotherapies, such as cisplatin, play a large role in cancer treatment. The development of resistance and treatment toxicity creates substantial barriers to disease control, yet. To enhance the therapeutic index of cisplatin-based chemotherapy, it is imperative to circumvent resistance and toxicity while optimizing tumor sensitization. One of the primary mechanisms by which cancer cells develop resistance to cisplatin is through upregulation of DNA repair pathways. In this review, we discuss the DNA damage response in the context of cisplatin-induced DNA damage. We describe the proteins involved in the pathways and their roles in resistance development. Common biomarkers for cisplatin resistance and their utilization to improve patient risk stratification and treatment personalization are addressed. Finally, we discuss some of the current treatments and future strategies to circumvent the development of cisplatin resistance.

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Section: Cisplatin Mechanism Of Action In Cancer Control and Toxicitymentioning

confidence: 99%

Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

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Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

Kiss

Xia

Acklin

2021

IJMS

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Alpelisib and Immunotherapy: A Promising Combination for Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck

Suleiman,

McGarrah,

Baral

et al. 2024

Cancer Reports

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BackgroundRecurrent squamous cell carcinoma (SCC) of the head and neck (SCCHN) remains a formidable clinical challenge despite available treatments. The phosphatidylinositol 3‐kinase (PI3K) pathway has been identified as a potential therapeutic target, and alpelisib, a selective PI3Kα inhibitor, has demonstrated efficacy in certain malignancies. Combining this targeted therapy with immunotherapy has been suggested in previous studies as a promising strategy to bolster the immune response against cancer.CasesA 69‐year‐old woman with locoregional recurrence of PIK3CA‐mutated SCC of the left maxilla and cervical nodal metastases. Several chemotherapeutic regimens, including cisplatin, docetaxel, 5FU, chemoradiotherapy, and mono‐immunotherapy, resulted in disease progression. Alpelisib combined with pembrolizumab led to a sustained response for 9 months. A 58‐year‐old man with recurrent metastatic PIK3CA‐mutated SCC of the oropharynx, involving the left lung, hilar, and mediastinal lymph nodes. Despite prior palliative radiation and platinum‐based chemotherapy with pembrolizumab and cetuximab, treatment with alpelisib and nivolumab resulted in a partial response. Severe hyperglycemia and rash led to treatment discontinuation.ConclusionOur findings highlight the potential of this innovative therapeutic combination, suggesting a need for further investigations in this setting.

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Bioinformatics approach combined with experimental verification reveals OAS3 gene implicated in paclitaxel resistance in head and neck cancer

Caglar,

Aytatli,

Barlak

et al. 2024

Head & Neck

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BackgroundThis study aimed to identify a candidate gene associated with paclitaxel (PTX) resistance and to evaluate functionally its biological role in the PTX‐resistant head and neck squamous cell carcinoma (HNSCC) cell lines and clinical specimens.MethodsMicroarray data series containing samples of different types of cancers resistant to PTX were analyzed and then a candidate gene associated with PTX resistance was identified using various bioinformatics tools. After the suppression of the target gene expression, changes in cell viability and colony‐forming ability were evaluated in PTX‐resistant FaDu and SCC‐9 cell lines.ResultsBioinformatics analyses of upregulated genes in PTX‐resistant cancer cells indicated that OAS3 was associated with PTX resistance. The downregulation of OAS3 expression significantly reduced the viability and colony‐forming capacity of PTX‐resistant SCC‐9 cells by inducing apoptosis and cell cycle arrest at G0/G1 phase.ConclusionsThe therapeutic targeting of OAS3 may resensitize PTX‐resistant HNSCC cells with high OAS3 expression to PTX treatment.

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Molecular Mechanisms of Chemotherapy Resistance in Head and Neck Cancers

Cited by 41 publications

References 121 publications

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

Alpelisib and Immunotherapy: A Promising Combination for Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck

Bioinformatics approach combined with experimental verification reveals OAS3 gene implicated in paclitaxel resistance in head and neck cancer

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