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Critical Reviews in Oncogenesis

Daniele Borsetto, Jordan Cheng, Karl Payne, Paul Nankivell, Nikolas Batis, Kanishka Rao, Shreerang Bhide, Feng Li, Yong Kim, Hisham Mehanna, David Wong
Head and neck squamous cell carcinoma (HNSCC) manifests in the mucosal epithelial lining of the oral cavity, oropharynx, hypopharynx, nasopharynx or larynx and has a tremendous disease burden worldwide. Smoking and alcohol consumption were once major risk factors, but HPV-associated infection has emerged as the major contributor to HNSCC occurrence in developed countries. Circulating biomarker evaluations in biofluids, also known as liquid biopsy, are an attractive alternative for cancer screening as they are minimally invasive, potentially low cost, and easily repeatable on a serial basis...
2018: Critical Reviews in Oncogenesis
Mengying Hong, Kejun Tang, Jing Qian, Hongyu Deng, Musheng Zeng, Shu Zheng, Kefeng Ding, Yushen Du, Ren Sun
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies in southern China and Southeast Asia. Unfortunately, 70% of NPC patients have locally advanced disease at the first diagnosis. Radiotherapy alone and concurrent chemoradiotherapy are important treatment approaches for NPC, but they have a limited effect on patients with locally advanced or distantly metastatic disease. 1-5 Nevertheless, the unique immune environment of the EBV-associated NPC provides rational targets for immunotherapy...
2018: Critical Reviews in Oncogenesis
Mo K Kang, Wei Chen, No-Hee Park
Grainyhead-Like 2 (GRHL2) was originally described as one of the three mammalian isoforms with sequence homology to Grainyhead (GRH) in Drosophila, which determines the cuticle formation in fruit flies. Earlier studies characterized GRHL2 as an epithelial-specific transcription factor that regulates epithelial morphogenesis and differentiation. Using a high-throughput proteomic approach, we discovered GRHL2 as a novel trans-regulator of the hTERT gene, which codes for the catalytic subunit of the human telomerase...
2018: Critical Reviews in Oncogenesis
Ki-Hyuk Shin, Reuben H Kim
Cancer stem cells (CSCs; also known as tumor-initiating cells) are a small population of cancer cells that retain characteristics similar to those of normal stem cells. CSCs are known to be responsible for metastasis, drug resistance, and cancer recurrence. Thus, controlling CSCs may provide an effective therapeutic intervention that inhibits tumor growth and aggressiveness. Despite the importance of targeting CSCs in cancer therapy, the detailed nature of oral CSCs remains underexplored. This article reviews the current understanding of oral CSCs, with emphasis on recent advances in novel signaling pathways involved in their stemness regulation...
2018: Critical Reviews in Oncogenesis
Christie Rodriguez-Ramirez, Jacques E Nör
Head and neck cancers are deadly diseases that are diagnosed annually in approximately half a million individuals worldwide. Growing evidence supporting a role for cancer stem cells (CSCs) in the pathobiology of head and neck cancers has led to increasing interest in identifying therapeutics to target these cells. Apart from the canonical tumor-suppressor functions of p53, emerging research supports a significant role for this protein in physiological stem cell and CSC maintenance and reprogramming. Therefore, p53 has become a promising target to sensitize head and neck CSCs to chemotherapy...
2018: Critical Reviews in Oncogenesis
Hassan Nasser, Maie St John
Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive disease with multiple mechanisms to impair immune-mediated recognition and control of tumor cell proliferation and metastasis. Based on successes experienced with cancer immunotherapy in the treatment of other solid tumors, considerable efforts are underway to develop immunotherapeutics that can enhance the host antitumor response to HNSCC. Promising results in preclinical studies and early clinical trials have been reported, prompting the FDA to approve the use of the immune checkpoint PD-1 receptor antagonist pembrolizumab for the treatment of platinum-refractory recurrent or metastatic HNSCC in 2016...
2018: Critical Reviews in Oncogenesis
Edward J Shillitoe
The pathogenesis of oral cancer is complex, and not all relevant factors involved in it have been determined. In particular, the role of the microbiota is not well understood because of difficulties in isolating and culturing its organisms. However, the recent development of metagenomic sequencing allows the discovery of all the DNA sequences in a specimen, and thus, the microbiome is now under intensive investigation. Studies of the bacteriome, the mycobiome, and the virome have revealed new organisms and have uncovered various differences between healthy persons and patients with oral cancer...
2018: Critical Reviews in Oncogenesis
H Helen Lin, Kirsten H Limesand, David K Ann
Salivary gland cancers (SGCs), categorized as head and neck cancers (HNCs), constitute about 6% of head and neck cancer diagnoses based on estimate by American Head and Neck Society. Salivary gland tumors originate from different glandular cell types and are thus morphologically diverse. These tumors arise from any of the three major and various minor salivary glands. The incidence of SGCs has slowly increased during the last four decades. The etiology of SGCs is mostly unknown; however, specific gene mutations are associated with certain types of salivary tumors...
2018: Critical Reviews in Oncogenesis
Andy Wai Kan Yeung, Amr El-Demerdash, Ioana Berindan-Neagoe, Atanas G Atanasov, Yuh-Shan Ho
Although numerous bibliometric studies have examined various aspects of cancer research, the landscape of scientific studies focusing on natural products in cancer research has not been characterized. Using the Web of Science Core Collection online database, we identify and analyze scientific articles on natural products in cancer-related research. English is the language of publication for 99% of articles. In general, annual citation count of an article increases quickly after publication, reaches a plateau in the second year, stays in this plateau for 10 yr, and then begins to fall...
2018: Critical Reviews in Oncogenesis
Anna Marzvanyan, Vicky Chen, Boshi Zhang, Greg Asatrian
Since the discovery of autophagy in the mid-2000s, the interest in autophagy-related processes within the scientific community has been burgeoning. Countless authors have investigated its function in cellular homeostasis, but arguably of higher importance is its role during pathology. Although primarily a catabolic process, in cancer cells autophagy has numerous downstream effects, being observed to be both pro- and anti-apoptotic. One of the primary factors mediating this differential role of autophagy is the accumulation or sequestration of reactive oxygen species (ROS)...
2018: Critical Reviews in Oncogenesis
Malina Xiao, Muhammad Zaeem Noman, Ludovic Menard, Andy Chevigne, Martyna Szpakowska, Manon Bosseler, Markus Ollert, Guy Berchem, Bassam Janji
Autophagy is a quality control process executed at the basal level in almost all cell types. However, in cancer cells, autophagy is activated by several stimuli, including hypoxia. Depending on tumor type, stage, and genetic context, autophagy is a double-edged sword. Autophagy promotes regression in newly established tumors; however, it supports tumor progression in well-established tumors by maintaining cancer cell survival under stress conditions. These data, in addition to the emerging role of autophagy in impairing antitumor immunity, have attracted significant interest in developing autophagy inhibitors as a new approach to cancer treatment...
2018: Critical Reviews in Oncogenesis
Benjamin Bonavida
The role of autophagy in the pathogenesis of various cancers has been well documented in many reports. Autophagy in cancer cells regulates cell proliferation, viability, invasion, epithelial-to-mesenchymal transition (EMT), metastasis, and responses to chemotherapeutic and immunotherapeutic treatment strategies. These manifestations are the result of various regulatory gene products that govern autophagic, biochemical, and molecular mechanisms. In several human cancer cell models, the presence of a dysregulated circuit-namely, NFκB/SNAIL/YY1/RKIP/PTEN-that plays a major role in the regulation of tumor cell unique characteristics just listed for autophagy-regulated activities...
2018: Critical Reviews in Oncogenesis
Yuhao Wang, Benjamin Bonavida
The complexities of molecular signaling in cancer cells have been hypothesized to mediate cross-network alterations of oncogenic processes such as uncontrolled cell growth, proliferation, acquisition of epithelial-to-mesenchymal transition (EMT) markers, and resistance to cytotoxic therapies. The two biochemically exclusive processes/proteins examined in the present review are the metastasis suppressor Raf-1 kinase inhibitory protein (RKIP) and the cell-intrinsic system of macroautophagy (hereafter referred to as autophagy)...
2018: Critical Reviews in Oncogenesis
Uma Maheswari, Sudha Rani Sadras
Autophagy, or self-eating, is a catabolic process that plays a crucial role in cellular homeostasis by carrying out bulk degradation of defective or superfluous proteins as well as worn-out organelles through a specialized structure, the autophagosome, which in turn fuses with the lysosome. Autophagy also alleviates cellular stress induced by nutrient deprivation, metabolic disturbance, hypoxia, and the like, by recycling intracellular constituents. This role of autophagy, to provide metabolic precursors especially upon starvation, might also contribute to the survival of cancer cells...
2018: Critical Reviews in Oncogenesis
Tianzhi Huang, Xiao Song, Yongyong Yang, Xuechao Wan, Angel A Alvarez, Namratha Sastry, Haizhong Feng, Bo Hu, Shi-Yuan Cheng
Autophagy is a catabolic program that is responsible for the degradation of dysfunctional or unnecessary proteins and organelles to maintain cellular homeostasis. Mechanistically, it involves the formation of double-membrane autophagosomes that sequester cytoplasmic material and deliver it to lysosomes for degradation. Eventually, the material is recycled back to the cytoplasm. Abnormalities of autophagy often lead to human diseases, such as neurodegeneration and cancer. In the case of cancer, increasing evidence has revealed the paradoxical roles of autophagy in both tumor inhibition and tumor promotion...
2018: Critical Reviews in Oncogenesis
Michael Grunert, Rebecca Kassubek, Burkhardt Danz, Burkhard Klemenz, Sebastian Hasslacher, Sebastien Stroh, Lukas Schneele, Julia Langhans, Stephanie Ströbele, Sara E Barry, Shaoxia Zhou, Klaus-Michael Debatin, Mike-Andrew Westhoff
The use of radiation is an essential part of both modern cancer diagnostic assessment and treatment. Next-generation imaging devices create 3D visualizations, allowing for better diagnoses and improved planning of precision treatment. This is particularly important for primary brain cancers such as diffuse intrinsic pontine glioma or the most common primary brain tumor, glioblastoma, because radiotherapy is often the only treatment modality that offers a significant improvement in survival and quality of life...
2018: Critical Reviews in Oncogenesis
Noel J Aherne, Brona M Murphy
Radiation therapy has been a cornerstone of cancer management for many decades and is an integral part of the multi-modality care of patients with brain tumors. The known serious side effects of radiation therapy on the head or central nervous system are uncommon and include radiation necrosis, microangiopathy, and progressive leukencephalopathy. In addition, there have been descriptions of radiation-induced tumors including sarcomas, gliomas, lymphomas, and carcinomas of the thyroid. Patients who have received radiation therapy of the head or face may rarely develop radiation-induced tumors, a majority of which are meningiomas, followed by radiation-induced gliomas (RIGs) and sarcomas...
2018: Critical Reviews in Oncogenesis
Elizabeth K Balcer-Kubiczek, John G Eley
Although modern radiation therapy delivers a localized distribution of ionizing energy that can be used to cure primary cancers for many patients, the inevitable radiation exposure to non-targeted normal tissue leads to a risk of a radiation-related new cancer. Modern therapies often produce a complex spectrum of secondary particles, both charged and uncharged, that must be considered both in their physical radiation transport throughout the patient and their potential to induce biological damage, which depends on the microscopic energy deposition from the cascade of primary, secondary, and downstream particles...
2018: Critical Reviews in Oncogenesis
Emiliya A Domina, Alex Philchenkov, Anna Dubrovska
Radiation therapy remains one of the most effective cancer treatments. Nevertheless, biology-driven personalized radiation therapy that enables treatment according to the biological characteristics of the individual tumors and normal tissues still needs to be implemented in the clinic. Understanding the mechanisms of radiation response in both tumors and normal tissues is necessary to develop reliable predictive biomarkers for tumor radioresistance and normal tissue toxicity as well as to exploit new therapeutic opportunities for tumor radiosensitization...
2018: Critical Reviews in Oncogenesis
Luksana Chaiswing, Heidi L Weiss, Rani D Jayswal, Daret K St Clair, Natasha Kyprianou
Radiation therapy (RT) is commonly used for the treatment of localized prostate cancer (PCa). However, cancer cells often develop resistance to radiation through unknown mechanisms and pose an intractable challenge. Radiation resistance is highly unpredictable, rendering the treatment less effective in many patients and frequently causing metastasis and cancer recurrence. Understanding the molecular events that cause radioresistance in PCa will enable us to develop adjuvant treatments for enhancing the efficacy of RT...
2018: Critical Reviews in Oncogenesis
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