Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies DOI Creative Commons
Rahul Bhattacharjee, Sabya Sachi Das,

Smruti Sudha Biswal

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2022, Volume and Issue: 174, P. 103675 - 103675

Published: April 4, 2022

Cervical cancer (CC), one of the major causes death women throughout world is primarily caused due to Human Papilloma Virus (HPV) 16 and 18. The early region (E) oncoproteins HPV are associated with etiopathogenesis contribute progression cancer. present article comprehensively discussed structural organization biological functions all E proteins their contribution CC an intent decipher pathological hallmarks relationship. Additionally, role in reference therapeutics will also be presented. A systematic search has been carried out for articles published PubMed database by using combinations different keywords Boolean operators (AND, OR, NOT) including cervical cancer, HPV, proteins, signaling. From analysis literature review, its apparent that contributor disease progression. E1, E2, E4 forms mainly viral integration, replication, transcription whereas E6 E7 act as oncoprotein E5 regulates cell proliferation, apoptosis, facilitates activity E7. were observed numerous signaling pathways PI3K/AKT, Wnt, Notch reasonably initiation malignancy, metastasis, drug resistance. Knowing interplay each protein CC, therapeutic significance elucidated. study observations demonstrate cause HPV-mediated a backbone most current approaches have targeted mediated action only. review illustrates well function regulation association several cellular pathways. provide clue on regulatory aspect these represent targeting could novel strategy CC. In particular, seemingly appears inhibition may better selective target delay reaffirms encourages future studies developing diagnostics, importantly strategies tackle related morbidity mortality.

Language: Английский

Head and neck squamous cell carcinoma DOI Creative Commons
Daniel E. Johnson, Barbara Burtness, C. René Leemans

et al.

Nature Reviews Disease Primers, Journal Year: 2020, Volume and Issue: 6(1)

Published: Nov. 26, 2020

Most head and neck cancers are derived from the mucosal epithelium in oral cavity, pharynx larynx known collectively as squamous cell carcinoma (HNSCC). Oral cavity generally associated with tobacco consumption, alcohol abuse or both, whereas increasingly attributed to infection human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative HPV-positive HNSCC. Despite evidence of histological progression cellular atypia through various degrees dysplasia, ultimately leading invasive HNSCC, most patients diagnosed late-stage without a clinically evident antecedent pre-malignant lesion. Traditional staging using tumour–node–metastasis system has been supplemented by 2017 AJCC/UICC system, which incorporates additional information relevant disease. Treatment is multimodal, consisting surgery followed chemoradiotherapy (CRT) for primary CRT cancers. The EGFR monoclonal antibody cetuximab used combination radiation where comorbidities prevent use cytotoxic chemotherapy. FDA approved immune checkpoint inhibitors pembrolizumab nivolumab treatment recurrent metastatic unresectable Elucidation molecular genetic landscape over past decade revealed new opportunities therapeutic intervention. Ongoing efforts aim integrate our understanding biology immunobiology identify predictive biomarkers that will enable delivery effective, least-toxic therapies. Head carcinomas (HNSCCs) originate commonly viral use. This Primer provides an overview epidemiology, pathogenesis HNSCCs different aetiologies effects cancer its on patient quality life.

Language: Английский

Citations

2802
NK cells for cancer immunotherapy DOI
Noriko Shimasaki, Amit Jain, Dario Campana

et al.

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(3), P. 200 - 218

Published: Jan. 6, 2020

Language: Английский

Citations

973
Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors DOI
Shona Hendry, Roberto Salgado,

Thomas Gevaert

et al.

Advances in Anatomic Pathology, Journal Year: 2017, Volume and Issue: 24(6), P. 311 - 335

Published: Aug. 2, 2017

Assessment of the immune response to tumors is growing in importance as prognostic implications this are increasingly recognized, and immunotherapies evaluated implemented different tumor types. However, many approaches can be used assess describe response, which limits efforts at implementation a routine clinical biomarker. In part 1 review, we have proposed standardized methodology tumor-infiltrating lymphocytes (TILs) solid tumors, based on International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. 2 discuss available evidence predictive value TILs common including carcinomas lung, gastrointestinal tract, genitourinary system, gynecologic head neck, well primary brain mesothelioma melanoma. The particularities emphases TIL assessment types discussed. propose adapted may standard against other compared. Standardization will help clinicians, researchers pathologists conclusively evaluate utility simple biomarker current era immunotherapy.

Language: Английский

Citations

672
HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management DOI Open Access
Matt Lechner, Jacklyn Liu, Liam Masterson

et al.

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(5), P. 306 - 327

Published: Feb. 1, 2022

Language: Английский

Citations

570
Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity DOI Creative Commons
Mikhail Binnewies, Adriana M. Mujal, Joshua L. Pollack

et al.

Cell, Journal Year: 2019, Volume and Issue: 177(3), P. 556 - 571.e16

Published: April 1, 2019

Language: Английский

Citations

519
PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers DOI Open Access
Mark Yarchoan, Lee A. Albacker,

Alexander C. Hopkins

et al.

JCI Insight, Journal Year: 2019, Volume and Issue: 4(6)

Published: March 21, 2019

BACKGROUND. PD-L1 expression and tumor mutational burden (TMB) have emerged as important biomarkers of response to immune checkpoint inhibitor (ICI) therapy. These each succeeded failed in predicting responders for different cancer types. We sought describe the landscape across spectrum ICI-responsive human cancers, determine relationship between expression, TMB, rates ICIs.

Language: Английский

Citations

464
Human Papillomavirus E6 and E7: The Cervical Cancer Hallmarks and Targets for Therapy DOI Creative Commons
Asmita Pal, Rita Kundu

Frontiers in Microbiology, Journal Year: 2020, Volume and Issue: 10

Published: Jan. 21, 2020

Human papillomavirus (HPV)-induced cervical cancer is a major health issue among women from the poorly/under-developed sectors of world. It accounts for high mortality rate, because its late diagnosis and poor prognosis. Initial establishment subsequent progression this form completely dependent on two oncogenes E6 E7, which expressed constitutively leading to tumorigenesis. Thus, manipulation these genes represent most successful therapy. In present article information structural, functional clinical dimensions E7 activity have been reviewed. The genome organisation protein structure discussed followed by their mechanism establish six hallmarks in tissues tumour propagation. later section review deals with different modes therapeutics function deregulating activity. Since are biomarkers cell ones driving progression, therapeutic approaches targeting proved be highly efficient terms focused removal abnormally propagating malignant cells. Therapeutics including forms vaccines advanced editing techniques suppress found successfully bring down population cells infected HPV. T-cell mediated immunotherapy another upcoming treatment eradicate HPV tumorigenic Additionally, using natural compounds plants or other repositories, i.e. phytotherapeutic also reviewed here, prove anticancer potential through inhibitory effects. repression any methods significant approach towards therapy, described details along an insight into signalling pathways molecular mechanistic action.

Language: Английский

Citations

453
Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer DOI Creative Commons
Qingzhu Jia, Wei Wu, Yuqi Wang

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Dec. 12, 2018

Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses 15 patients with non-small lung cancer (NSCLC). This revealed that immune microenvironment has high heterogeneity such intratumoral regional variation is as large inter-personal variation. While local total mutational burden (TMB) associated T-cell clonal expansion, anti-tumor cytotoxicity does not directly correlate neoantigen abundance. Together, these findings caution against immunological signatures can be predicted solely TMB or microenvironmental analysis a single locus biopsy.

Language: Английский

Citations

394
Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments DOI
Benjamin Solomon, Richard J. Young, Danny Rischin

et al.

Seminars in Cancer Biology, Journal Year: 2018, Volume and Issue: 52, P. 228 - 240

Published: Jan. 30, 2018

Language: Английский

Citations

391
Immunogenic neoantigens derived from gene fusions stimulate T cell responses DOI
Wei Yang, Ken-Wing Lee, Raghvendra M. Srivastava

et al.

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(5), P. 767 - 775

Published: April 22, 2019

Language: Английский

Citations

327