Pub Date : 2019-06-07DOI: 10.5772/INTECHOPEN.85988
C. Lorz, C. Segrelles, Ricardo Errazquin, R. García-Escudero
Over the last two decades, a number of high-throughput technologies (genome-and proteome-based) have been developed and applied on different cancer types such as squamous cell carcinomas (SCCs) arising from aerodigestive and genitourinary tracts. These analyses, when comprehensively utilized, have clearly con-tributed to a better understanding of the molecular hallmarks, oncogenic pathways and immunological features of SCCs. This chapter aims to describe the SCCs most important molecular aberrations as well as their molecular classification, highlight-ing the commonalities and differences among them, independent of their body site origin. The most frequently altered oncogene is PIK3CA, involved in the PI3K/ AKT/mTOR pathway and frequently activated in many human cancers. However, alterations in the cell-cycle control TP53 gene occur in the vast majority of SCCs. New possible molecular therapies, common to all SCCs, are discussed in light of a comprehensive, panSCC analysis.
{"title":"Comprehensive Molecular Characterization of Squamous Cell Carcinomas","authors":"C. Lorz, C. Segrelles, Ricardo Errazquin, R. García-Escudero","doi":"10.5772/INTECHOPEN.85988","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.85988","url":null,"abstract":"Over the last two decades, a number of high-throughput technologies (genome-and proteome-based) have been developed and applied on different cancer types such as squamous cell carcinomas (SCCs) arising from aerodigestive and genitourinary tracts. These analyses, when comprehensively utilized, have clearly con-tributed to a better understanding of the molecular hallmarks, oncogenic pathways and immunological features of SCCs. This chapter aims to describe the SCCs most important molecular aberrations as well as their molecular classification, highlight-ing the commonalities and differences among them, independent of their body site origin. The most frequently altered oncogene is PIK3CA, involved in the PI3K/ AKT/mTOR pathway and frequently activated in many human cancers. However, alterations in the cell-cycle control TP53 gene occur in the vast majority of SCCs. New possible molecular therapies, common to all SCCs, are discussed in light of a comprehensive, panSCC analysis.","PeriodicalId":416359,"journal":{"name":"Squamous Cell Carcinoma - Hallmark and Treatment Modalities","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127967073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-05-31DOI: 10.5772/INTECHOPEN.85650
A. Jain
Oral carcinogenesis is a molecular and histological multistage process featuring genetic and phenotypic molecular markers which involves enhanced function of several protooncogenes, oncogenes and/or the deactivation of tumor suppressor genes, resulting in the over activity of growth factors and its cell surface receptors, which could enhance messenger signaling intracellularly, and/or leads to the increased production of transcription factors. Alone oncogenes are not responsible for carcinogenesis, genes having tumor suppressor activity, leads to a phenotypic change in cell which is responsible for increased cell proliferation, loss of cellular cohesion, and the ability to infiltrate local tissue and spread to distant sites. Understanding the molecular interplay of both onco and tumor genes will allow more accurate diagnosis and assessment of prognosis, which might lead the way for novel approaches to treatment.
{"title":"Molecular Pathogenesis of Oral Squamous Cell Carcinoma","authors":"A. Jain","doi":"10.5772/INTECHOPEN.85650","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.85650","url":null,"abstract":"Oral carcinogenesis is a molecular and histological multistage process featuring genetic and phenotypic molecular markers which involves enhanced function of several protooncogenes, oncogenes and/or the deactivation of tumor suppressor genes, resulting in the over activity of growth factors and its cell surface receptors, which could enhance messenger signaling intracellularly, and/or leads to the increased production of transcription factors. Alone oncogenes are not responsible for carcinogenesis, genes having tumor suppressor activity, leads to a phenotypic change in cell which is responsible for increased cell proliferation, loss of cellular cohesion, and the ability to infiltrate local tissue and spread to distant sites. Understanding the molecular interplay of both onco and tumor genes will allow more accurate diagnosis and assessment of prognosis, which might lead the way for novel approaches to treatment.","PeriodicalId":416359,"journal":{"name":"Squamous Cell Carcinoma - Hallmark and Treatment Modalities","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132785942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-04-16DOI: 10.5772/INTECHOPEN.86041
S. Boyle, Z. Kopecki
Cutaneous squamous cell carcinoma (cSCC) accounts for 25% of cutaneous malignancies diagnosed in the Caucasian population. Surgical removal in combination with radio- and chemotherapy is an effective treatment; however, prognosis for patients suffering from aggressive cSCC is still relatively poor. Increasing prevalence coupled with high mortality and morbidity in aggressive metastatic forms of cSCC highlights the need for development of novel targeted therapeutics. Metastasis is a complex process requiring dramatic reorganization of the cell cytoskeleton. Recent studies have highlighted the importance of mechanical forces and actin dynamics in cancer cells’ intrinsic ability to invade adjacent tissues, intravasate into vasculature, and ultimately metastasize. Tight regulation of the biochemical and mechanical properties of the actin cytoskeleton drives cellular processes involved in cSCC progression including polarity establishment, morphogenesis, and motility. Here we will provide a short introduction to disease pathogenesis, give an overview of the role of key regulatory proteins governing the mechanical forces and actin dynamics critical to cSCC progression, and describe the contribution of actin remodeling and actomyosin signaling to cSCC progression. We will also discuss how targeting protein regulating mechanical force and actin dynamics may have clinical utility in development of novel treatment modalities for patients suffering from aggressive cSCC.
{"title":"Mechanical Force and Actin Dynamics during Cutaneous Squamous Cell Carcinoma (cSCC) Progression: Opportunities for Novel Treatment Modalities","authors":"S. Boyle, Z. Kopecki","doi":"10.5772/INTECHOPEN.86041","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.86041","url":null,"abstract":"Cutaneous squamous cell carcinoma (cSCC) accounts for 25% of cutaneous malignancies diagnosed in the Caucasian population. Surgical removal in combination with radio- and chemotherapy is an effective treatment; however, prognosis for patients suffering from aggressive cSCC is still relatively poor. Increasing prevalence coupled with high mortality and morbidity in aggressive metastatic forms of cSCC highlights the need for development of novel targeted therapeutics. Metastasis is a complex process requiring dramatic reorganization of the cell cytoskeleton. Recent studies have highlighted the importance of mechanical forces and actin dynamics in cancer cells’ intrinsic ability to invade adjacent tissues, intravasate into vasculature, and ultimately metastasize. Tight regulation of the biochemical and mechanical properties of the actin cytoskeleton drives cellular processes involved in cSCC progression including polarity establishment, morphogenesis, and motility. Here we will provide a short introduction to disease pathogenesis, give an overview of the role of key regulatory proteins governing the mechanical forces and actin dynamics critical to cSCC progression, and describe the contribution of actin remodeling and actomyosin signaling to cSCC progression. We will also discuss how targeting protein regulating mechanical force and actin dynamics may have clinical utility in development of novel treatment modalities for patients suffering from aggressive cSCC.","PeriodicalId":416359,"journal":{"name":"Squamous Cell Carcinoma - Hallmark and Treatment Modalities","volume":"354 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115925598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-03-25DOI: 10.5772/INTECHOPEN.85545
L. Dewit, A. Cats, G. Beets
Treatment of squamous cell carcinoma of the anus has evolved over the last 5 decades from radical surgery to combined chemoradiation therapy. Radiation treatment techniques have dramatically improved with the development of more powerful computers, algorithms and treatment machines. The clinical impact of the modern radiation treatment techniques, such as intensity-modulated radiotherapy and volumetric modulated arc therapy, is discussed. The standard-of-care regimen still is concurrent Mitomycin C, 5-fluorouracil and high-dose radiation, as was conceived 45 years ago. Variants of this schedule are discussed in this chapter. International guidelines have been generated and implemented. Whereas concurrent chemoradiation therapy is the treatment of choice for locally advanced tumors, early tumors are probably adequately controlled with either reduced dose chemoradiation therapy or radiation therapy alone. Prognostic factors, such as high-risk human papillomavirus, epidermal growth factor receptor and immune response, will be highlighted. The role of surgery in primary care is limited to local excision of T1N0 tumors ≤ 1 cm of the anal margin. Salvage radical surgery is limited to locoregional recurrent, non-metastasized and resectable tumors after chemoradiation therapy. In addition, new treatment modalities, such as targeted therapy and immunotherapy, will be discussed. Current research aims at refining prognostic subgroups to further individualize treatment strategy, implementing quality assurance protocols in international trials and investigating the molecular profile of squamous cell carcinoma of the anus, in order to identify new treatment avenues. This will hopefully change the landscape of anal cancer treatment in the future.
{"title":"Evolving Concepts toward Individualized Treatment of Squamous Cell Carcinoma of the Anus","authors":"L. Dewit, A. Cats, G. Beets","doi":"10.5772/INTECHOPEN.85545","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.85545","url":null,"abstract":"Treatment of squamous cell carcinoma of the anus has evolved over the last 5 decades from radical surgery to combined chemoradiation therapy. Radiation treatment techniques have dramatically improved with the development of more powerful computers, algorithms and treatment machines. The clinical impact of the modern radiation treatment techniques, such as intensity-modulated radiotherapy and volumetric modulated arc therapy, is discussed. The standard-of-care regimen still is concurrent Mitomycin C, 5-fluorouracil and high-dose radiation, as was conceived 45 years ago. Variants of this schedule are discussed in this chapter. International guidelines have been generated and implemented. Whereas concurrent chemoradiation therapy is the treatment of choice for locally advanced tumors, early tumors are probably adequately controlled with either reduced dose chemoradiation therapy or radiation therapy alone. Prognostic factors, such as high-risk human papillomavirus, epidermal growth factor receptor and immune response, will be highlighted. The role of surgery in primary care is limited to local excision of T1N0 tumors ≤ 1 cm of the anal margin. Salvage radical surgery is limited to locoregional recurrent, non-metastasized and resectable tumors after chemoradiation therapy. In addition, new treatment modalities, such as targeted therapy and immunotherapy, will be discussed. Current research aims at refining prognostic subgroups to further individualize treatment strategy, implementing quality assurance protocols in international trials and investigating the molecular profile of squamous cell carcinoma of the anus, in order to identify new treatment avenues. This will hopefully change the landscape of anal cancer treatment in the future.","PeriodicalId":416359,"journal":{"name":"Squamous Cell Carcinoma - Hallmark and Treatment Modalities","volume":"50 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127276621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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