Review
Oncology
Bayley G. Matthews, Nikola A. Bowden, Michelle W. Wong-Brown
Summary: High-grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer, with a stagnant overall survival rate over the past three decades. Chemoresistance remains a major challenge in treating HGSOC, and may be driven by epigenetic modifications. Identifying epigenetic changes in chemoresistant HGSOC allows for the development of targeted therapies to improve outcomes.
Article
Oncology
Zhao Cheng, Hasan Mirza, Darren P. Ennis, Philip Smith, Lena Morrill Gavarro, Chishimba Sokota, Gaia Giannone, Theodora Goranova, Thomas Bradley, Anna Piskorz, Michelle Lockley, Baljeet Kaur, Naveena Singh, Laura A. Tookman, Jonathan Krell, Jacqueline McDermott, Geoffrey Macintyre, Florian Markowetz, James D. Brenton, Iain A. McNeish
Summary: Late-stage and early-stage high-grade serous carcinomas (HGSCs) of the ovary exhibit highly similar patterns of mutation and copy-number alterations. However, late-stage HGSCs show distinct copy-number signature exposures consistent with whole-genome duplication. Further analysis is needed to determine whether these differences reflect genuine biological disparities between early-stage and late-stage disease or simply markers of evolutionary fitness over time.
CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Duhita Sengupta, Asima Mukhopadhyay, Kaushik Sengupta
Summary: Extensive research in the past twenty years has greatly contributed to our understanding of the roles of lamins in maintaining nuclear architecture and genome organization, which are significantly altered in cancer formation. Alterations in the expression and distribution of lamin A/C have been consistently observed in the development of almost all types of human tumors. One characteristic of cancer cells is their inability to repair DNA damage, leading to genomic instability and increased sensitivity to chemotherapy. In this study, we found elevated levels of lamins in OVCAR3 cells, a high-grade ovarian serous carcinoma cell line, as well as altered DNA damage repair machinery. Furthermore, we identified differentially expressed genes associated with cellular proliferation and chemoresistance in ovarian carcinoma induced by etoposide, with lamin A showing particularly elevated expression. Our findings suggest that elevated lamin A plays a role in neoplastic transformation in high-grade ovarian serous cancer through a combination of HR and NHEJ mechanisms.
Article
Multidisciplinary Sciences
Akira Yokoi, Mayu Ukai, Takao Yasui, Yasuhide Inokuma, Kim Hyeon-Deuk, Juntaro Matsuzaki, Kosuke Yoshida, Masami Kitagawa, Kunanon Chattrairat, Mikiko Iida, Taisuke Shimada, Yumehiro Manabe, I-Ya Chang, Eri Asano-Inami, Yoshihiro Koya, Akihiro Nawa, Kae Nakamura, Tohru Kiyono, Tomoyasu Kato, Akihiko Hirakawa, Yusuke Yoshioka, Takahiro Ochiya, Takeshi Hasegawa, Yoshinobu Baba, Yusuke Yamamoto, Hiroaki Kajiyama
Summary: Cancer cell-derived extracellular vesicles (EVs) could be potential targets for disease biomarkers due to their unique protein profiles. Analysis of small EVs (sEVs) and medium/large EVs (m/lEVs) revealed that both subtypes had distinct proteomic characteristics. Specific sEV proteins (FRa, Claudin-3, and TACSTD2) for high-grade serous ovarian carcinoma (HGSOC) were identified, while no candidates were found for m/lEVs. Additionally, a microfluidic device using polyketone-coated nanowires (pNWs) was developed for efficient sEV isolation and showed specific detectability in cancer patients and predicted clinical status.
Review
Oncology
Ikuo Konishi, Kaoru Abiko, Takuma Hayashi, Koji Yamanoi, Ryusuke Murakami, Ken Yamaguchi, Junzo Hamanishi, Tsukasa Baba, Noriomi Matsumura, Masaki Mandai
Summary: Epithelial ovarian cancer, particularly high-grade serous carcinoma (HGSC), is a deadly gynecological malignancy in women, often diagnosed at advanced stages with peritoneal dissemination. Chromosomal instability and epigenetic dynamics are believed to drive cancer development in the fallopian tube and peritoneal metastasis in HGSC, highlighting the importance of targeting clonal evolution and the peritoneal microenvironment in developing novel strategies for prevention and treatment.
JOURNAL OF GYNECOLOGIC ONCOLOGY
(2022)
Editorial Material
Multidisciplinary Sciences
Craig M. Bielski, Barry S. Taylor
Summary: Genomic instability is a characteristic of cancer, but exploiting this feature to selectively target cancer cells remains a major challenge in cancer biology with significant implications for drug development.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Tibor A. Zwimpfer, Ori Tal, Franziska Geissler, Ricardo Coelho, Natalie Rimmer, Francis Jacob, Viola Heinzelmann-Schwarz
Summary: High-grade serous ovarian cancers (HGSOCs) arise from the fallopian tube and harbor TP53 gene mutations, while low-grade serous ovarian cancers (LGSOCs) have different features and are considered a distinct subtype. Treatment for LGSOCs is limited due to a lack of separate trial data, but current understanding suggests slow tumor growth and precursors from serous borderline ovarian tumors. Therapeutic decisions are guided by characteristics such as estrogen receptor positivity and specific mutations, leading to maintenance with endocrine treatment or targeted therapies. Ongoing trials are exploring the use of MEK inhibitors in combination with hormonal treatments for LGSOCs.
CANCER TREATMENT REVIEWS
(2023)
Article
Oncology
Romina Silva, Kate Glennon, Michael Metoudi, Bruce Moran, Sofia Salta, Karen Slattery, Ann Treacy, Terri Martin, Jacqui Shaw, Peter Doran, Lydia Lynch, Carmen Jeronimo, Antoinette S. Perry, Donal J. Brennan
Summary: Resistance to platinum-based chemotherapy is a major cause of death in high-grade serous ovarian cancer (HGSOC). This study identified specific DNA methylation changes that can predict platinum resistance in HGSOC. The results showed that hypermethylation of NKAPL and hypomethylation of APOBEC3A were associated with relapsed HGSOC. In vitro experiments also demonstrated that demethylation of NKAPL promoter increased platinum sensitivity.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Puja Dey, Kentaro Nakayama, Sultana Razia, Masako Ishikawa, Tomoka Ishibashi, Hitomi Yamashita, Kosuke Kanno, Seiya Sato, Tohru Kiyono, Satoru Kyo
Summary: This study successfully developed an in vitro carcinogenic model of LGSOCs and found that the mutations of KRAS and PIK3CA play a causative role in LGSOC tumorigenesis. Simultaneous activation of the KRAS/ERK and PIK3CA/AKT signaling pathways is essential for LGSOC development.
Article
Oncology
Mikhail S. Chesnokov, Imran Khan, Yeonjung Park, Jessica Ezell, Geeta Mehta, Abdelrahman Yousif, Linda J. Hong, Ronald J. Buckanovich, Akimasa Takahashi, Ilana Chefetz
Summary: High-grade serous ovarian carcinoma (HGSOC) has a poor prognosis due to high recurrence rate and acquired chemoresistance. Inhibition of MEK1/2 may suppress cancer growth but also promote stem-like properties in HGSOC cells, suggesting the need for combination therapy targeting cancer stem cells.
Review
Oncology
Amal A. Al-Dossary, Essam A. Tawfik, Adaugo C. Isichei, Xin Sun, Jiahe Li, Abdullah A. Alshehri, Munther Alomari, Fahad A. Almughem, Ahmad M. Aldossary, Hussein Sabit, Abdulaziz M. Almalik
Summary: This review discusses the role of natural extracellular vesicles (EVs) in high-grade serous ovarian cancer (HGSOC) and the advantages of using engineered EV-mimetic nanoparticles as a delivery vehicle. It also highlights the challenges and promising directions in the clinical translation of these systems.
Review
Biochemistry & Molecular Biology
Paula Punzon-Jimenez, Victor Lago, Santiago Domingo, Carlos Simon, Aymara Mas
Summary: High-grade serous ovarian carcinoma (HGSOC) is the most common form of epithelial ovarian carcinoma, and its early diagnosis still relies on traditional methods. Research on its etiopathogenesis provides new insights for finding early detection methods.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Dane Cheasley, Abhimanyu Nigam, Magnus Zethoven, Sally Hunter, Dariush Etemadmoghadam, Timothy Semple, Prue Allan, Mark S. Carey, Marta L. Fernandez, Amy Dawson, Martin Kobel, David G. Huntsman, Cecile Le Page, Anne-Marie Mes-Masson, Diane Provencher, Neville Hacker, Yunkai Gao, David Bowtell, Anna deFazio, Kylie L. Gorringe, Ian G. Campbell
Summary: Low-grade serous ovarian carcinoma (LGSOC) is linked with poor response to chemotherapy, emphasizing the importance of genomic analysis to identify new therapeutic targets. A comprehensive study of LGSOC patients revealed potential driver aberrations and protein expressions that could impact disease outcomes and treatment responses.
(c) 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
JOURNAL OF PATHOLOGY
(2021)
Review
Oncology
Tania Moujaber, Rosemary L. Balleine, Bo Gao, Ida Madsen, Paul R. Harnett, Anna DeFazio
Summary: Low-grade serous ovarian cancer (LGSC) is a distinct subtype of ovarian cancer, accounting for about 10% of serous carcinomas. Patients with LGSC typically present at a younger age and have a longer clinical course compared to other subtypes. The primary treatment for LGSC is debulking surgery followed by platinum/taxane chemotherapy. However, the response rates to platinum-based chemotherapy in LGSC are low, leading to the investigation of alternative therapies such as endocrine maintenance therapy and combination targeted therapies.
ENDOCRINE-RELATED CANCER
(2022)
Article
Multidisciplinary Sciences
Elaine Stur, Sara Corvigno, Mingchu Xu, Ken Chen, Yukun Tan, Sanghoon Lee, Jinsong Liu, Emily Ricco, Daniel Kraushaar, Patricia Castro, Jianhua Zhang, Anil K. Sood
Summary: This study represents the first comprehensive analysis of spatial transcriptomics in high-grade serous ovarian carcinoma using intact tumor tissue. The study revealed extensive differences in tumor composition between poor and excellent responders to chemotherapy, with spatial interactions potentially playing a larger role in chemo-responsiveness.
Article
Gastroenterology & Hepatology
Kit Curtius, Misha Kabir, Ibrahim Al Bakir, Chang Ho Ryan Choi, Juanda L. Hartono, Michael Johnson, James E. East, James O. Lindsay, Roser Vega, Siwan Thomas-Gibson, Janindra Warusavitarne, Ana Wilson, Trevor A. Graham, Ailsa Hart
Summary: This study identified that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing advanced neoplasia. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator can support treatment decision-making.
Article
Biotechnology & Applied Microbiology
Carina C. D. Joe, Jinlin Jiang, Thomas Linke, Yuanyuan Li, Sofiya Fedosyuk, Gaurav Gupta, Adam Berg, Rameswara R. Segireddy, David Mainwaring, Amar Joshi, Paul Cashen, Byron Rees, Nitin Chopra, Piergiuseppe Nestola, Jonathan Humphreys, Sarah Davies, Nick Smith, Scott Bruce, Dennis Verbart, Daan Bormans, Carol Knevelman, Mark Woodyer, Lee Davies, Lisa Cooper, Maria Kapanidou, Nicole Bleckwenn, Daniel Pappas, Teresa Lambe, Daniel C. Smith, Catherine M. Green, Raghavan Venkat, Adam J. Ritchie, Sarah C. Gilbert, Richard Turner, Alexander D. Douglas
Summary: In response to the COVID-19 pandemic, we have developed an effective vaccine based on novel manufacturing technologies, allowing for large-scale production and distributed manufacturing to ensure international supply security and cost-effectiveness.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Review
Gastroenterology & Hepatology
Kit Curtius, Samir Gupta, C. Richard Boland
Summary: Lynch syndrome is an autosomal dominant familial condition caused by a pathogenic variant in a DNA mismatch repair gene, predisposing carriers to various cancers. This review aims to discuss the pathogenesis, clinical presentation, differential diagnosis, and clinical strategies for detection and management of Lynch syndrome. Lynch syndrome tumors have a unique pathogenesis resulting in hypermutation, microsatellite instability, and high immunogenicity. Understanding the pathogenesis of Lynch syndrome informs current strategies for detection and clinical management, and guides future areas for clinical innovation.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Oncology
Ganga Gopinathan, Chiara Berlato, Anissa Lakhani, Ludmila Szabova, Colin Pegrum, Ana-Rita Pedrosa, Florian Laforets, Eleni Maniati, Frances R. Balkwill
Summary: This article investigates mechanisms of resistance to the VEGF receptor inhibitor cediranib in high-grade serous ovarian cancer (HGSOC), and defines rational combination therapies. The study found that combining anti-IL6 or anti-PD-1 with VEGFR inhibitors may increase their activity and prolong disease-free survival in HGSOC patients.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Medicine, Research & Experimental
Altar M. Munis, Benjamin Wright, Frederic Jackson, Helen Lockstone, Stephen C. Hyde, Catherine M. Green, Deborah R. Gill
Summary: Understanding pulmonary diseases requires robust culture models. However, current models fail to generate reliable disease models. Recently, researchers developed a new culture platform for studying and correcting rare lung diseases. Comparison of gene expression profiles revealed that this culture model is remarkably similar to human alveolar cells, indicating its clinical relevance.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Oncology
Michael-John Devilin, Rowan Miller, Florian Laforets, Panoraia Kotantaki, Dale W. Garsed, Rebecca Kristeleit, David D. Bowtell, Jacqueline McDermott, Eleni Maniati, Frances R. Balkwill
Summary: The tumor microenvironment (TME) of clear-cell ovarian cancer (CCOC) was analyzed in this study, revealing differences in immune cell populations, collagen matrix, and cytokine expression between different areas of the tumor. Advanced CCOC showed increased fibroblasts and a more complex collagen matrix compared to early CCOC. Differences in immune cell populations, collagen matrix, and cytokine expression were also observed between different genetic subtypes of CCOC. Increased infiltration of specific T cell subpopulations was associated with decreased overall survival.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Genetics & Heredity
James V. Talwar, David Laub, Meghana S. Pagadala, Andrea Castro, McKenna Lewis, Georg E. Luebeck, Bryan R. Gorman, Cuiping Pan, Frederick N. Dong, Kyriacos Markianos, Craig C. Teerlink, Julie Lynch, Richard Hauger, Saiju Pyarajan, Philip S. Tsao, Gerald P. Morris, Rany M. Salem, Wesley K. Thompson, Kit Curtius, Maurizio Zanetti, Hannah Carter
Summary: Autoimmunity and cancer are two different aspects of immune dysfunction, characterized by breakdowns in self-tolerance and impaired immune surveillance, respectively. This study shows that MHC-I autoimmune-risk alleles are associated with a delayed age of melanoma diagnosis and decreased risk of developing melanoma. The findings suggest that these alleles modulate melanoma risk that is not accounted for by current risk scores.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Gastroenterology & Hepatology
Roshani V. Patel, Kit Curtius, Ripple Man, Jordan Fletcher, Victoria Cuthill, Susan K. Clark, Alexander C. von Roon, Andrew Latchford
Summary: This study analyzed data from 249 patients with familial adenomatous polyposis (FAP) and found that 76% of patients developed at least one pouch body adenoma, with 16% developing an advanced pouch body lesion. The cumulative incidence of advanced lesions in the pouch body and cuff after 10 years was 2.8% and 6.4%, respectively. The presence of adenomas before the 10-year point was associated with an increased risk of subsequent development of advanced lesions. These findings can guide personalized surveillance for FAP patients.
Article
Cell Biology
Syed A. Mian, Celine Philippe, Eleni Maniati, Pantelitsa Protopapa, Tiffany Bergot, Marion Piganeau, Travis Nemkov, Doriana Di Bella, Valle Morales, Andrew J. Finch, Angelo D'Alessandro, Katiuscia Bianchi, Jun Wang, Paolo Gallipoli, Shahram Kordasti, Anne Sophie Kubasch, Michael Cross, Uwe Platzbecker, Daniel H. Wiseman, Dominique Bonnet, Delphine G. Bernard, John G. Gribben, Kevin Rouault-Pierre
Summary: Patients with myelodysplastic syndrome and ring sideroblasts (MDS-RS) suffer from symptomatic anemia due to ineffective erythropoiesis caused by SF3B1 mutations. Mis-splicing of COASY induced by these mutations affects heme biosynthesis and erythropoiesis. Supplementation with COASY substrate may serve as a potential treatment for anemia in MDS-RS patients.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
E. H. Puttock, E. J. Tyler, M. Manni, E. Maniati, C. Butterworth, M. Burger Ramos, E. Peerani, P. Hirani, V. Gauthier, Y. Liu, G. Maniscalco, V. Rajeeve, P. Cutillas, C. Trevisan, M. Pozzobon, M. Lockley, J. Rastrick, H. Laeubli, A. White, O. M. T. Pearce
Summary: This study demonstrates that the extracellular matrix (ECM) can influence the phenotype of tumor-associated macrophages (TAMs). It reveals an association between the composition of tumor ECM, a specific TAM population, and poor prognosis. By developing a decellularized tissue model, the authors show that the ECM can induce transcriptional profiles in macrophages similar to those found in human tissue. The findings suggest that targeting the tumor ECM in cancer therapies may improve macrophage phenotype and their regulation of immunity.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Microbiology
Caitlin Guccione, Daniel McDonald, Rebecca Fielding-Miller, Kit Curtius, Rob Knight
NATURE MICROBIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Bingxin Lu, Kit Curtius, Trevor A. Graham, Ziheng Yang, Chris P. Barnes
Summary: Phylogenetic trees based on copy number profiles from multiple samples of a patient are helpful to understand cancer evolution. We developed a new maximum likelihood method, CNETML, to infer phylogenies from such data. CNETML is the first program to jointly infer the tree topology, node ages, and mutation rates from total copy numbers of longitudinal samples. Our simulations show that CNETML performs well on copy numbers relative to ploidy and slightly violated model assumptions.
Article
Biochemical Research Methods
Brian Johnson, Yubo Shuai, Jason Schweinsberg, Kit Curtius
Summary: Measuring evolution itself is difficult due to experimental constraints and the dynamic nature of body systems. However, using DNA sequencing datasets at single-cell resolution, researchers can reconstruct past evolution and gain a better understanding of dynamics prior to detectable disease.
Meeting Abstract
Gastroenterology & Hepatology
Steven D. Ma, Caitlin Guccione, Kristen Linnemeyer, Madeline Greytak, Aws Hasan, Joshua Rubin, Philip Weissbrod, Bernd Schnabl, Kit Curtius, Rena Yadlapati
Meeting Abstract
Gastroenterology & Hepatology
Steven D. Ma, Caitlin Guccione, Kristen Linnemeyer, Madeline Greytak, Aws Hasan, Joshua Rubin, Philip Weissbrod, Bernd Schnabl, Kit Curtius, Rena Yadlapati