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Molecular Oncology

Juan Miguel Baquero, Carlos Benítez-Buelga, Victoria Fernández, Miguel Urioste, Jose Luis García-Giménez, Rosario Perona, Javier Benítez, Ana Osorio
Single Nucleotide Polymorphisms (SNPs) in DNA glycosylase genes involved in the Base Excision Repair (BER) pathway can modify breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We previously found that SNP rs34259 in the uracil-DNA glycosylase gene (UNG) might decrease ovarian cancer risk in BRCA2 mutation carriers. In the present study we validated this finding in a larger series of familial breast and ovarian cancer patients to gain insights into how this UNG variant exerts its protective effect...
February 12, 2019: Molecular Oncology
Malay K Sannigrahi, Cheerneni S Srinivas, Nilesh Deokate, Sabyasachi Rakshit
Cadherin-23 (Cdh23), a long chain non-classical cadherin, exhibits strong homophilic and heterophilic binding. The physiological relevance of strong heterophilic binding with protocadherin-15 at neuroepithelial tip links is well-studied. However, the role of Cdh23 homodimers in physiology is less understood, despite its widespread expression at the cell-boundaries of various human and mouse tissues, including kidney, muscle, testes, and heart. Here, we performed immunofluorescence studies that revealed that Cdh23 is present as distinct puncta at the cell-cell boundaries of cancer cells...
February 12, 2019: Molecular Oncology
Lorena Verduci, Sabrina Strano, Yosef Yarden, Giovanni Blandino
Circular RNAs (circRNAs) comprise an emerging new class of endogenous RNAs expressed abundantly by the eukaryotic transcriptome. They are characterized by a covalently closed loop structure, resulting in RNA molecules that are more stable than linear RNAs. A growing number of studies indicate that circRNAs play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. The molecular events determined by circRNA activity, the CircRNA code, involve other types of non-coding RNA molecules, primarily microRNAs, long non-coding RNAs and RNA-binding proteins...
February 4, 2019: Molecular Oncology
Nicole M Reilly, Luca Novara, Federica Di Nicolantonio, Alberto Bardelli
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. Therapies that take advantage of defects in DNA repair pathways have been explored in the context of breast, ovarian, and other tumor types, but not yet systematically in CRC. At present, only immune checkpoint blockade therapies have been FDA approved for use in mismatch repair deficient colorectal tumors. Here, we discuss how systematic identification of alterations in DNA repair genes could provide new therapeutic opportunities for CRCs...
February 3, 2019: Molecular Oncology
Ruoxi Hong, Weimin Zhang, Xi Xia, Kai Zhang, Yan Wang, Mengjiao Wu, Jiawen Fan, Jinting Li, Wen Xia, Fei Xu, Jie Chen, Shusen Wang, Qimin Zhan
BRCA1 has been implicated in modulating metabolism via transcriptional regulation. However, direct metabolic targets of BRCA1 and the underlying regulatory mechanisms are still unknown. Here, we identified several metabolic genes, including the gene which encodes glutamate-oxaloacetate transaminase 2 (GOT2), a key enzyme for aspartate biosynthesis, which are repressed by BRCA1. We report that BRCA1 forms a co-repressor complex with ZBRK1 that coordinately represses GOT2 expression via a ZBRK1 recognition element in the promoter of GOT2...
February 3, 2019: Molecular Oncology
Elena Garralda, Rodrigo Dienstmann, Alex Piris, Irene Braña, Jordi Rodon, Josep Tabernero
Cancer treatment has made significant strides towards the promise of personalized medicine. Recent scientific advances have shown that there are numerous genetic deregulations that are common in multiple cancer types, raising the possibility of developing drugs targeting those deregulations irrespective of the tumour type. Precision cancer medicine was born out of accumulated evidence matching targeted agents with these tumour molecular deregulations. At the same time, the therapeutic armamentarium is rapidly increasing and the number of new drugs (including immune-oncology agents) entering drug development continues to rise...
January 30, 2019: Molecular Oncology
Wasfi Alrawashdeh, Richard Jones, Laurent Dumartin, Tomasz P Radon, Pedro R Cutillas, Roger M Feakins, Branko Dmitrovic, Ihsan Ekin Demir, Guralp O Ceyhan, Tatjana Crnogorac-Jurcevic
Perineural invasion (PNI) is a common and characteristic feature of pancreatic ductal adenocarcinoma (PDAC) that is associated with poor prognosis, tumor recurrence, and generation of pain. However, the molecular alterations in cancer cells and nerves within PNI have not previously been comprehensively analysed. Here, we describe our proteomic analysis of the molecular changes underlying neuro-epithelial interactions in PNI using liquid chromatography-mass spectrometry (LC-MS/MS) in microdissected PNI and non-PNI cancer, as well as invaded and non-invaded nerves from formalin-fixed, paraffin-embedded PDAC tissues...
January 28, 2019: Molecular Oncology
Zhiqiang Wu, Minghan Qiu, Zeyun Mi, Maobin Meng, Yu Guo, Xiangli Jiang, Jiaping Fang, Hui Wang, Jinlin Zhao, Zhuang Liu, Dong Qian, Zhiyong Yuan
Lung cancer is the most common cancer and the leading cause of cancer-related death worldwide; hence, it is imperative that the mechanisms underlying the malignant properties of lung cancer be uncovered in order to efficiently treat this disease. Increasing evidence has shown that WT1-interacting protein (WTIP) plays important roles both physiologically and pathologically in humans; however, the role of WTIP in cancer is unknown. Here, we investigated the role and mechanism of WTIP in cell proliferation and tumorigenesis of non-small cell lung cancer (NSCLC)...
January 28, 2019: Molecular Oncology
Davide Serrano, Bernardo Bonanni, Karen Brown
The constant increase of cancer incidence and the huge costs of new treatments make cancer prevention a crucial goal in order to maintain sustainable public health systems across the world. Carcinogenesis is a multi-step process, which allows time for active intervention with natural or synthetic agents to stop or reverse the pathological process. Cancer prevention medicine can be considered to be treatment of premalignant cells or preneoplastic conditions. Clearly such interventions require well-defined risk classification so that personalized strategies and specific treatments can be applied to cohorts with a documented increased cancer risk, and not to the general population as a whole...
January 28, 2019: Molecular Oncology
Ingemar Ernberg
Educational initiatives in cancer research have to align with the needs of patients, individuals at risk, healthcare systems, and public health organisations. The above interests demand strong translational interactions between basic research, clinical/prevention research, and entrepreneurship. The resulting synergy between these three entities is expected to stimulate identification of unresolved issues in cancer biology, as well as unmet needs in diagnostics, treatment, and prevention. It will also encourage the development of international research collaborations and, in turn, improve access to innovative research infrastructures...
January 24, 2019: Molecular Oncology
Wladyslaw Januszewicz, Rebecca C Fitzgerald
Early detection, including cancer screening and surveillance, is emerging as one of the most important topics in modern oncology. As symptomatic presentation remains the predominant route to cancer diagnosis, there is a growing interest in developing techniques to detect the disease at an early, curative stage. Moreover, growing understanding of cancer biology has paved the way for prevention studies with the focus on therapeutic interventions for premalignant conditions. Where there is a recognisable precursor stage, such as a colorectal adenoma or Barrett's metaplasia, the removal of abnormal tissue prevents the development of cancer and enables stratification of the patient to a high-risk group requiring further surveillance...
January 24, 2019: Molecular Oncology
Joakim Dillner
The rapidly increasing incidence and mortality of cancer calls for a focused effort to increase the effect of cancer-prevention efforts. In the area of early detection, there are major differences in the preventive impact of implemented screening policies, even when solid, evidence-based international recommendations are issued. Studies are needed to determine why evidence-based interventions are not used and to research why effects are less than predicted by solid research on the subject. Currently, population-based screening is recommended only for 3 forms of cancer (cervical, breast, and colorectal cancer), but, given the increasing cancer burden, efforts are required to facilitate the discovery of new biomarkers for screening, as well as the identification of barriers to implementation of new cancer screening discoveries...
January 24, 2019: Molecular Oncology
Tao Liu, Hailong Zhang, Sha Yi, Lubing Gu, Muxiang Zhou
MDM4 and topoisomerase IIα (TOP2A) are over-expressed in various human cancers. MDM4 acts as an oncoprotein which promotes cancer progression by inhibiting tumor suppressor p53. As a DNA replication- and cell division-regulating enzyme, TOP2A is the main target of many anticancer therapy regimens; however, the exact role of TOP2A in cancer remains elusive. Herein, we report that MDM4 and TOP2A bind to each other and are mutually upregulated at the post-translational level, leading to TOP2A protein stabilization, inhibition of p53, and increased tumor-cell proliferation...
January 23, 2019: Molecular Oncology
Yidong Zhou, Yaping Xu, Yuhua Gong, Yanyan Zhang, Yaping Lu, Changjun Wang, Ru Yao, Peng Li, Yanfang Guan, Jiayin Wang, Xuefeng Xia, Ling Yang, Xin Yi, Qiang Sun
Noninvasive circulating tumor DNA (ctDNA) can be used to predict breast cancer recurrence and prognosis. In this study, we detected 226 and 114 somatic variants in tumor DNA from 70 primary breast cancer (PBC) patients (98.59%) and ctDNA from 48 patients (67.61%), respectively. Gene frequencies of tumor DNA and ctDNA significantly correlated (R2 =0.9532, p<0.0001), and tumor-derived variants were detectable in the blood of 43 patients. ctDNA was more often detected in locally advanced/metastatic and non-luminal patients...
January 23, 2019: Molecular Oncology
Christopher P Wild, Carolina Espina, Linda Bauld, Bernardo Bonanni, Hermann Brenner, Karen Brown, Joakim Dillner, David Forman, Ellen Kampman, Mef Nilbert, Karen Steindorf, Hans Storm, Paolo Vineis, Michael Baumann, Joachim Schüz
The case for cancer prevention in Europe is the same as for all other parts of the world. The number of cancers is increasing, driven by demographic change and evolution in the exposure to risk factors, while the cost of treating patients is likewise spiralling. Estimations suggest that around 40% of cancers in Europe could be prevented if current understanding of risk and protective factors was translated into effective primary prevention, with further reductions in cancer incidence and mortality by screening, other approaches to early detection, and potentially medical prevention...
January 22, 2019: Molecular Oncology
Bo Zhang, Linling Wang, Qi Zhang, Youyou Yan, Hong Jiang, Runlei Hu, Xinglu Zhou, Xingguo Liu, Jianguo Feng, Nengming Lin
Ibrutinib is a small molecule drug that targets Bruton's tyrosine kinase in B-cell malignancies, and is highly efficient at killing mantle cell lymphoma and chronic lymphocytic leukemia. However, the anti-cancer activity of Ibrutinib against solid tumors, such as non-small cell lung cancer (NSCLC), remains low. To improve the cytotoxicity of Ibrutinib towards lung cancer, we synthesized a series of Ibrutinib derivatives, of which Ibr-7 exhibited superior anti-cancer activity to Ibrutinib, especially against epithelial growth factor receptor (EGFR) wild-type NSCLC cell lines...
January 20, 2019: Molecular Oncology
Julio E Celis, Manuel Heitor
Today, cancer is a significant challenge for society, healthcare systems, and the growing number of affected patients and their families. This article argues that new paradigms and conditions for responsible science and innovation policy across the EU require the collective action of Research & Development institutions, a system approach to health systems, higher education, and patient organizations, and new initiatives to encourage international cooperation across an enlarged Europe; no single country can successfully fight the disease(s) on its own...
January 18, 2019: Molecular Oncology
Alexander M M Eggermont, Giovanni Apolone, Michael Baumann, Carlos Caldas, Julio E Celis, Francesco de Lorenzo, Ingemar Ernberg, Ulrik Ringborg, John Rowell, Josep Tabernero, Emile Voest, Fabien Calvo
Cancer Core Europe is a European legal alliance consisting of seven leading cancer centres - most of them Comprehensive Cancer Centres (CCCs) - with a single portal system to engage in various research projects with partners. Cancer Core Europe was established to create a sustainable, high-level, shared research infrastructure platform hosting research collaborations and taskforces (data sharing, clinical trials, genomics, immunotherapy, imaging, education and training and legal & ethical issues), with a controlled expansion agenda...
January 18, 2019: Molecular Oncology
Christian H Brandts
In many countries a majority of cancer patients are not treated at Comprehensive Cancer Centers (CCCs). Even for those that are, parts of the treatment or follow-up may be carried out in local community hospitals or in private practices. How to assure quality in cancer care and create innovation? How to integrate decentralized versus centralized patient care, education, and cancer research? Outlined here is a 360° view of outreach to include all stake holders - most importantly patients and their families, patient advocacy groups, health care providers, health insurers, and policy makers...
January 18, 2019: Molecular Oncology
Francesco de Lorenzo, Kathi Apostolidis
There is an urgent need for solutions to the economic and social inequalities in cancer care that still exist in many European countries. Patient preferences, "big data", mobile digital technology, and molecular and genomic profiling are among the innovative research topics that connect cancer patients to comprehensive cancer centres, and link translational research to cancer diagnosis, treatment, and care. The question is whether Europe can deliver the complex infrastructure needed for universal coverage and equitable access to cancer care...
January 18, 2019: Molecular Oncology
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