Cell death in photodynamic therapy: From oxidative stress to anti-tumor immunity Publication date: Available online 8 August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer Author(s): Claire Donohoe, Mathias O. Senge, Luís G. Arnaut, Lígia C. Gomes-da-Silva Abstract Photodynamic therapy is a promising approach for cancer treatment that relies on the administration of a photosensitizer followed by tumor illumination. The generated oxidative stress may activate multiple mechanism of cell death which are counteracted by cells through adaptive stress responses that target homeostasis rescue. The present renaissance of PDT was leveraged by the acknowledgment that this therapy has an immediate impact locally, in the illumination volume, but that subsequently it may elicit immune responses with systemic impact. The investigation of the mechanisms of cell death under the oxidative stress of PDT is of paramount importance to understand how the immune system is activated and, ultimately, to make PDT a more appealing/relevant therapeutic option.

From squamous intraepithelial lesions to cervical cancer: Circulating microRNAs as potential biomarkers in cervical carcinogenesis Publication date: Available online 6 August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer Author(s): Fernanda Costa Brandão Berti, Amanda Salviano-Silva, Helen Cristina Beckert, Karen Brajão de Oliveira, Gabriel Adelman Cipolla, Danielle Malheiros Abstract Despite Human Papillomavirus (HPV) essential role in cervical carcinogenesis, other factors are required for cancer establishment, like miRNAs. Such molecules present a complex biogenesis, being diversely distributed across tissues and biological fluids, as cell-free miRNAs or miRNAs present in extracellular vesicles (EV). After HPV infection, an interplay between HPV and the miRNA network occurs in cervical cells. As the virus persists and cellular transformation occurs, specific patterns of miRNA expression are found in different stages of cervical disease. Thus, defining promising miRNAs/specific miRNA signatures - especially circulating miRNAs - represents an interesting strategy for screening (diagnosis, prognosis, etc.) those stages. Despite the limited number of studies investigating circulating miRNAs in distinct biological fluids, accumulating data have pointed some promising candidates, both as cell-free or EV-derived miRNAs. Here we highlight some of these promising non-invasive biomarkers and bring attention to the urgent need for efforts in this field. Graphical abstract

Microbial carcinogenesis: Lactic acid bacteria in gastric cancer Publication date: Available online 5 August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer Author(s): Karla Vinasco, Hazel M. Mitchell, Nadeem O. Kaakoush, Natalia Castaño-Rodríguez Abstract While Helicobacter pylori is a fundamental risk factor, gastric cancer (GC) aetiology involves combined effects of microbial (both H. pylori and nonH. pylori), host and environmental factors. Significant differences exist between the gastric microbiome of those with gastritis, intestinal metaplasia and GC, suggesting that dysbiosis in the stomach is dynamic and correlates with progression to GC. Most notably, a consistent increase in abundance of lactic acid bacteria (LAB) has been observed in GC patients including Streptococcus, Lactobacillus, Bifidobacterium and Lactococcus. This review summarises how LAB can influence GC by a number of mechanisms that include supply of exogenous lactate —a fuel source for cancer cells that promotes inflammation, angiogenesis, metastasis, epithelial-mesenchymal transition and immune evasion—, production of reactive oxygen species and N-nitroso compounds, as well as anti-H. pylori properties that enable colonization by other nonH. pylori carcinogenic pathobionts.

Diverse mechanisms of PARP inhibitor resistance in ovarian cancer Publication date: Available online 2 August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer Author(s): Matthew John Wakefield, Ksenija Nesic, Olga Kondrashova, Clare L. Scott

The AP-1 transcriptional complex: Local switch or remote command? Publication date: August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1872, Issue 1 Author(s): Fabienne Bejjani, Emilie Evanno, Kazem Zibara, Marc Piechaczyk, Isabelle Jariel-Encontre Abstract The ubiquitous family of AP-1 dimeric transcription complexes is involved in virtually all cellular and physiological functions. It is paramount for cells to reprogram gene expression in response to cues of many sorts and is involved in many tumorigenic processes. How AP-1 controls gene transcription has largely remained elusive till recently. The advent of the “omics” technologies permitting genome-wide studies of transcription factors has however changed and improved our view of AP-1 mechanistical actions. If these studies confirm that AP-1 can sometimes act as a local transcriptional switch operating in the vicinity of transcription start sites (TSS), they strikingly indicate that AP-1 principally operates as a remote command binding to distal enhancers, placing chromatin architecture dynamics at the heart of its transcriptional actions. They also unveil novel constraints operating on AP-1, as well as novel mechanisms used to regulate gene expression via transcription-pioneering-, chromatin-remodeling- and chromatin accessibility maintenance effects.

Bacterial biofilms as a potential contributor to mucinous colorectal cancer formation Publication date: August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1872, Issue 1 Author(s): Shan Li, Maikel P. Peppelenbosch, Ron Smits Abstract A prominent mucinous phenotype is observed in 10–15% of all colorectal cancers (CRCs). They are associated with a proximal location, and more commonly observed among tumors with mismatch repair defects and a promoter CpG methylator phenotype. However, none of these features has been clearly linked mechanistically to this mucinous subtype. Here, we propose that bacterial biofilms could represent a currently unappreciated contributor to mucinous CRC formation. The colonic microbiome and biofilms in particular, are emerging as important factors in tumor initiation and progression. Intriguingly, biofilms preferentially accompany proximal tumors, suggesting that there may be a direct mechanistic link with mucinous CRCs.

Neuroendocrine regulation of cholangiocarcinoma: A status quo review Publication date: August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1872, Issue 1 Author(s): Meng Sha, Jie Cao, Han-yong Sun, Ying Tong, Qiang Xia Abstract Increasing studies have demonstrated that neuroendocrine system is involved in the development and progression of cholangiocarcinoma. The neuroendocrine hormones, neurotransmitters and neuropeptides regulate cholangiocarcinoma via affecting pathophysiology of tumor cells. The developing interaction and interplay between neuroendocrine-associated factors and tumor cells provide novel insights into neural control of tumorigenesis and reveal potential therapeutic effect on patients with cholangiocarcinoma. Herein we reviewed the latest findings and achievements which demonstrate the close interactions between neuroendocrine regulation and progression of cholangiocarcinoma. Also, future therapeutic approaches targeting neuroendocrine-associated factors are discussed which may help improve management and treatment of cholangiocarcinoma.

Defective mitosis-linked DNA damage response and chromosomal instability in liver cancer Publication date: August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1872, Issue 1 Author(s): Maryam Tahmasebi-Birgani, Hossein Ansari, Vinicio Carloni Abstract Hepatocellular carcinoma (HCC), the most common form of liver cancer, represents a health problem in hepatic viruses-eradicating era because obesity, type 2 diabetes, and nonalcoholic steatohepatitis (NASH) are considered emerging pathogenic factors. Metabolic disorders underpin mitotic errors that lead to numerical and structural chromosome aberrations in a significant proportion of cell divisions. Here, we review that genomically unstable HCCs show evidence for a paradoxically DNA damage response (DDR) which leads to ongoing chromosome segregation errors. The understanding of DDR induced by defective mitoses is crucial to our ability to develop or improve liver cancer therapeutic strategies.

Clinical validity of saliva and novel technology for cancer detection Publication date: August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1872, Issue 1 Author(s): Karolina Elżbieta Kaczor-Urbanowicz, Fang Wei, Shannon Liu Rao, Jinseok Kim, Heebum Shin, Jordan Cheng, Michael Tu, David T.W. Wong, Yong Kim Abstract Cancer, a local disease at an early stage, systemically evolves as it progresses by triggering alterations in surrounding microenvironment, disturbing immune surveillance and further disseminating its molecular contents into circulation. This pathogenic characteristic of cancer makes the use of biofluids such as blood/serum/plasma, urine, tear and cerebrospinal fluids credible surrogates harboring tumor tissue-derived molecular alterations for the detection of cancer. Most importantly, a number of recent reports have credentialed the clinical validity of saliva for the detection of systemic diseases including cancers. In this review, we discussed the validity of saliva as credible biofluid and clinical sample type for the detection of cancers. We have presented the molecular constituents of saliva that could mirror the systemic status of our body and recent findings of salivaomics associated with cancers. Recently, liquid biopsy to detect cancer-derived circulating tumor DNA has emerged as a credible cancer-detection tool with potential benefits in screening, diagnosis and also risk management of cancers. We have further presented the clinical validity of saliva for liquid biopsy of cancers and a new technology platform based on electrochemical detection of cancer-derived ctDNA in saliva with superior sensitivity and point-of-care potential. The clinical utilities of saliva for the detection of cancers have been evidenced, but biological underpinning on the existence of molecular signatures of cancer-origin in saliva, such as via exosomal distribution, should be addressed in detail.

From genetics to signaling pathways: molecular pathogenesis of esophageal adenocarcinoma Publication date: August 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1872, Issue 1 Author(s): Ravindran Caspa Gokulan, Monica T. Garcia-Buitrago, Alexander I. Zaika Abstract Esophageal adenocarcinoma (EAC) has one of the fastest rising incidence rates in the U.S. and many other Western countries. One of the unique risk factors for EAC is gastroesophageal reflux disease (GERD), a chronic digestive condition in which acidic contents from the stomach, frequently mixed with duodenal bile, enter the esophagus resulting in esophageal tissue injury. At the cellular level, progression to EAC is underlined by continuous DNA damage caused by reflux and chronic inflammatory factors that increase the mutation rate and promote genomic instability. Despite recent successes in cancer diagnostics and treatment, EAC remains a poorly treatable disease. Recent research has shed new light on molecular alterations underlying progression to EAC and revealed novel treatment options. This review focuses on the genetic and molecular studies of EAC. The molecular changes that occur during the transformation of normal Barrett’s esophagus to esophageal adenocarcinoma are also discussed.