Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers

Ortiz-Cuarán, Sandra; Bouaoud, Jebrane; Karabajakian, Andy; Fayette, Jérôme; Saintigny, Pierre

doi:10.3389/fonc.2021.614332

Cited by 36 publications

(29 citation statements)

References 284 publications

(463 reference statements)

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“…Thus, one single strategy might not be sufficient, and increased insights to the resistance mechanisms as well as identification of biomarkers will help to design novel and optimized therapeutic strategies, which either direct against tumor cells and/or modulate tumor microenvironment. These issues are also discussed in several recent excellent reviews [3,[137][138][139].…”

Section: Discussionmentioning

confidence: 98%

Targeting Stress-Response Pathways and Therapeutic Resistance in Head and Neck Cancer

Bos¹,

Ratti²,

Harada³

2021

Front. Oral. Health

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Head and neck cancer is the sixth leading cancer worldwide; head and neck squamous cell carcinoma (HNSCC) accounts for more than 90% of incident cases. In the US, cases of HNSCC associated with human papillomavirus (HPV) have been growing in proportion amongst a younger demographic with superior outcomes to the same treatments, relative to cases associated with tobacco. Yet failures to improve the long-term prognosis of advanced HNSCC over the last three decades persist in part due to intrinsic and acquired mechanisms of resistance. Deregulation of the pathways to respond to stress, such as apoptosis and autophagy, often contributes to drug resistance and tumor progression. Here we review the stress-response pathways in drug response and resistance in HNSCC to explore strategies to overcome these resistance mechanisms. We focus on the mechanisms of resistance to current standard cares, such as chemotherapy (i.e., cisplatin), radiation, and cetuximab. Then, we discuss the strategies to overcome these resistances, including novel combinations and immunotherapy.

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Section: Discussionmentioning

confidence: 98%

Targeting Stress-Response Pathways and Therapeutic Resistance in Head and Neck Cancer

Bos¹,

Ratti²,

Harada³

2021

Front. Oral. Health

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“…Targeted therapies have made a major impact on the management of HNSCC patients. Several promising therapeutic targets are being explored for HNSCC, but it is beyond the scope of the present article to include all of these, and therefore, recently published articles on this topic are cited [184][185][186]. The most promising targeted therapy is the inhibition of EGF-based cellular signaling mediated by EGFR binding mAb, cetuximab.…”

Section: Egfr Targeted Therapymentioning

confidence: 99%

Immunosuppressive microenvironment in oral cancer: implications for cancer immunotherapy

et al. 2021

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Head and neck squamous cell carcinoma (HNSCC) is a relatively widespread cancer with high mortality rates. Many patients with locally advanced disease are treated with combinations of surgery, radiation, and chemotherapy, while others are considered incurable and develop recurrent/metastatic(R/M) disease. Despite these treatment modalities, the 5-year survival rate of HNSCC has remained at 50% due to limited treatment options in patients with recurrent disease. Immunotherapy has been shown to induce durable responses in R/M patients, but only a minority of patients currently respond. A major hurdle in tumor immunotherapy is identifying the non-responders and markers to predict resistance in patients who at first responded to the therapy. In HNSCC patients, the tumor microenvironment (TME) assumes a vital role to either diminish or augment immune responses. There is an urgent need for extensive studies to be undertaken to better understand how tumor cells escape immune surveillance and resist immune attack. In this review, the impact of TME on the efficiency of immunotherapy, addressing the factors that mediate therapy resistance are highlighted. The composition of the TME encompassing the immunosuppressive cells including myeloid-derived suppressor cell (MDSC), regulatory T cells (Treg), mesenchymal stem cell (MSC), cancer-associated fibroblast (CAF), and tumor-associated macrophages (TAMs) and intrinsic factors like hypoxia, reactive oxygen species (ROS),extracellular matrix (ECM), angiogenesis, and epithelial-mesenchymal transition (EMT), how this debilitates immunosurveillance, and also discuss existing and potential strategies aimed at targeting these cellular and molecular TME components are reviewed. Understanding the interactions between the TME and immunotherapy is not only important in dissevering the mechanisms of action of immunosuppression but also offers scope for developing newer strategies to improve the competence of current immunotherapies.

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“…However, in most cases, the response is only partial and often leads to acquired resistance followed by tumor regrowth. This demonstrates the urgent need to better understand the tumor microenvironment in order to propose targeted therapy that could significantly improve the quality and life expectancy of patients with HNSCC in the future [18].…”

Section: Introductionmentioning

confidence: 99%

Long Intergenic Non-Coding RNAs in HNSCC: From “Junk DNA” to Important Prognostic Factor

Kozłowska

Kolenda

Poter

et al. 2021

Cancers

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Head and neck squamous cell carcinoma is one of the most common and fatal cancers worldwide. Even a multimodal approach consisting of standard chemo- and radiotherapy along with surgical resection is only effective in approximately 50% of the cases. The rest of the patients develop a relapse of the disease and acquire resistance to treatment. Especially this group of individuals needs novel, personalized, targeted therapy. The first step to discovering such solutions is to investigate the tumor microenvironment, thus understanding the role and mechanism of the function of coding and non-coding sequences of the human genome. In recent years, RNA molecules gained great interest when the complex character of their impact on our biology allowed them to come out of the shadows of the “junk DNA” label. Furthermore, long non-coding RNAs (lncRNA), specifically the intergenic subgroup (lincRNA), are one of the most aberrantly expressed in several malignancies, which makes them particularly promising future diagnostic biomarkers and therapeutic targets. This review contains characteristics of known and validated lincRNAs in HNSCC, such as XIST, MALAT, HOTAIR, HOTTIP, lincRNA-p21, LINC02487, LINC02195, LINC00668, LINC00519, LINC00511, LINC00460, LINC00312, and LINC00052, with a description of their prognostic abilities. Even though much work remains to be done, lincRNAs are important factors in cancer biology that will become valuable biomarkers of tumor stage, outcome prognosis, and contribution to personalized medicine.

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Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers

Cited by 36 publications

References 284 publications

Targeting Stress-Response Pathways and Therapeutic Resistance in Head and Neck Cancer

Targeting Stress-Response Pathways and Therapeutic Resistance in Head and Neck Cancer

Immunosuppressive microenvironment in oral cancer: implications for cancer immunotherapy

Long Intergenic Non-Coding RNAs in HNSCC: From “Junk DNA” to Important Prognostic Factor

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