Widespread expression of Sonic hedgehog (Shh) and Nrf2 in patients treated with cisplatin predicts outcome in resected tumors and are potential therapeutic targets for HPV-negative head and neck cancer

Noman, Abu Shadat Mohammod; Parag, Rashed R; Rashid, Muhammad Imran; Rahman, MK; Chowdhury, Ali Asgar; Sultana, Afrin; Jerin, Chandsultana; Siddiqua, Ayesha; Rahman, Lutfur; Shirin, Afsana; Mahmud, Reaz; Akther, Sonam; Shil, Rajib; Hossain, Ikram; Alam, Sharmin; Chowdhury, Arfina; Hasan, A. B. M. Toufique; Bithy, Shammy; Aklima, Jannatul; Rahman, Mohammad Ashiqur; Chowdhury, Nabila; Banu, Tahmina; Karakas, Bedri; Yeger, Herman; Farhat, Walid A.; Islam, Shariful

doi:10.1177/1758835920911229

Cited by 19 publications

(13 citation statements)

References 40 publications

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“…HO-1, the Nrf2-targeted gene, was also elevated in cisplatin-resistant HNNC patients. Knockdown of Nrf2 reversed the sphere-forming efficiency that marks the cancer stem cell characteristics in FaDu cells [157]. Inhibition of Nrf2 by artesunate leading to a reversal of the ferroptosis resistance in cisplatin-resistant HNC cells has been reported [158].…”

Section: Targeting the Prx Antioxidant System In Hncmentioning

confidence: 99%

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Huang

Pan

2020

Oxidative Medicine and Cellular Longevity

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Head and neck cancer is a highly genetic and metabolic heterogeneous collection of malignancies of the lip, oral cavity, salivary glands, pharynx, esophagus, paranasal sinuses, and larynx with five-year survival rates ranging from 12% to 93%. Patients with head and neck cancer typically present with advanced stage III, IVa, or IVb disease and are treated with comprehensive modality including chemotherapy, radiotherapy, and surgery. Despite advancements in treatment modality and technique, noisome recurrence, invasiveness, and resistance as well as posttreatment complications severely influence survival rate and quality of life. Thus, new therapeutic strategies are urgently needed that offer enhanced efficacy with less toxicity. ROS in cancer cells plays a vital role in regulating cell death, DNA repair, stemness maintenance, metabolic reprogramming, and tumor microenvironment, all of which have been implicated in resistance to chemo-/radiotherapy of head and neck cancer. Adjusting ROS generation and elimination to reverse the resistance of cancer cells without impairing normal cells show great hope in improving the therapeutic efficacy of chemo-/radiotherapy of head and neck cancer. In the current review, we discuss the pivotal and targetable redox-regulating system including superoxide dismutases (SODs), tripeptide glutathione (GSH), thioredoxin (Trxs), peroxiredoxins (PRXs), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/keap1), and mitochondria electron transporter chain (ETC) complexes and their roles in regulating ROS levels and their clinical significance implicated in chemo-/radiotherapy of head and neck cancer. We also summarize several old drugs (referred to as the non-anti-cancer drugs used in other diseases for a long time) and small molecular compounds as well as natural herbs which effectively modulate cellular ROS of head and neck cancer to synergize the efficacy of conventional chemo-/radiotherapy. Emerging interdisciplinary techniques including photodynamic, nanoparticle system, and Bio-Electro-Magnetic-Energy-Regulation (BEMER) therapy are promising measures to broaden the potency of ROS modulation for the benefit of chemo-/radiotherapy in head and neck cancer.

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Section: Targeting the Prx Antioxidant System In Hncmentioning

confidence: 99%

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Huang

Pan

2020

Oxidative Medicine and Cellular Longevity

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“…As shown by Noman et al. ( 16 ) for an early diagnosis and prognosis of HNSCC, it is necessary to validate and explore the prognostic values of the key genes of the cancer. They used The Cancer Genome Atlas (TCGA) database analysis and performed the experimental validation of the widespread expression of Sonic hedgehog (Shh) and Nrf2 genes in HNSCC patients treated with cisplatin.…”

Section: Resultsmentioning

confidence: 99%

“…However, high expression of this gene is indispensable for oral SCC progression ( 77 ) and adaptation to nutrient deprivation and hypoxia ( 78 ), and may inhibit apoptosis. The other two genes, Nrf2 and Itga6, known to be promoting factors of chemoresistance, are overexpressed in the non-responders ( 15 , 16 ). The non-responders also showed overexpression of INMT and MYOM3, but their function in HNSCC remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Three out of four reviewed genetic studies conducted research on groups of >50 patients ( 14 – 16 ), and one study analyzed a smaller group of <30 patients ( 13 ). Nevertheless, the latter study used an external group (n = 8 patients) to validate their model and received approximately 75.0% sensitivity and 100% specificity for an iCHT response prediction.…”

Section: Discussionmentioning

confidence: 99%

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Predictive Biomarkers for Response and Toxicity of Induction Chemotherapy in Head and Neck Cancers

Boguszewicz

2022

Front. Oncol.

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This review focuses on the molecular biology of head and neck squamous cell carcinomas and presents current and emerging biomarkers of the response of patients to induction chemotherapy. The usefulness of genes, proteins, and parameters from diagnostic clinical imaging as well as other clinicopathological parameters is thoroughly discussed. The role of induction chemotherapy before radiotherapy or before chemo-radiotherapy is still debated, as the data on its efficacy are somehow confusing. Despite the constant improvement of treatment protocols and the introduction of new cytostatics, there is still no consensus regarding the use of induction chemotherapy in the treatment of head and neck cancer, with the possible exception of larynx preservation. Such difficulties indicate that potential future treatment strategies should be personalized. Personalized medicine, in which individual tumor genetics drive the selection of targeted therapies and treatment plans for each patient, has recently emerged as the next generation of cancer therapy. Early prediction of treatment outcome or its toxicity may be highly beneficial for those who are at risk of the development of severe toxicities or treatment failure—a different treatment strategy may be applied to these patients, sparing them unnecessary pain. The literature search was carried out in the PubMed and ScienceDirect databases as well as in the selected conference proceedings repositories. Of the 265 articles and abstracts found, only 30 met the following inclusion criteria: human studies, analyzing prediction of induction chemotherapy outcome or toxicity based on the pretreatment (or after the first cycle, if more cycles of induction were administered) data, published after the year 2015. The studies regarding metastatic and recurrent cancers as well as the prognosis of overall survival or the outcome of consecutive treatment were not taken into consideration. As revealed from the systematic inspection of the papers, there are over 100 independent parameters analyzed for their suitability as prognostic markers in HNSCC patients undergoing induction chemotherapy. Some of them are promising, but usually they lack important features such as high specificity and sensitivity, low cost, high positive predictive value, clinical relevance, short turnaround time, etc. Subsequent studies are necessary to confirm the usability of the biomarkers for personal medicine.

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“…Goto et al recently showed that increased expression of ATP Binding Cassette Subfamily B Member 1 (ABCB1, commonly known as MDR1) and NRF2 are associated with doxorubicin resistance of CD44 + CD133 + cells, but not in case of CD44 + and CD44 + CD133 − cells [ 153 ]. Noman et al recently reported that high expression of Sonic hedgehog and NRF2 correlates with induced stem cell-like characteristics and contributes to chemoresistance of HNSCC cells [ 154 ]. A very recent study showed that dexamethasone can induce chemosensitization of CSCs through reduced expression of NRF2 and consequently increased levels of ROS, but only after the treatment with gemcitabine and 5-fluorouracil [ 155 ].…”

Section: The Role Of Nrf2 In Cancer Stem Cellsmentioning

confidence: 99%

Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response

et al. 2022

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Oxidative stress and its end-products, such as 4- hydroxynonenal (HNE), initiate activation of the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)/KEAP1 signaling pathway that plays a crucial role in the maintenance of cellular redox homeostasis. However, an involvement of 4-HNE and NRF2 in processes associated with the initiation of cancer, its progression, and response to therapy includes numerous, highly complex events. They occur through interactions between cancer and stromal cells. These events are dependent on many cell-type specific features. They start with the extent of NRF2 binding to its cytoplasmic repressor, KEAP1, and extend to the permissiveness of chromatin for transcription of ARE-containing genes that are NRF2 targets. This review will explore epigenetic molecular mechanisms of NRF2 transcription through the specific molecular anatomy of its promoter. It will explain the role of NRF2 in cancer stem cells, with respect to cancer therapy resistance. Additionally, it also discusses NRF2 involvement at the cross-roads of communication between tumor associated inflammatory and stromal cells, which is also an important factor involved in the response to therapy.

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Widespread expression of Sonic hedgehog (Shh) and Nrf2 in patients treated with cisplatin predicts outcome in resected tumors and are potential therapeutic targets for HPV-negative head and neck cancer

Cited by 19 publications

References 40 publications

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Predictive Biomarkers for Response and Toxicity of Induction Chemotherapy in Head and Neck Cancers

Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response

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