Editorial Material
Medicine, Research & Experimental
Jonas Schwickert, Franziska M. Zickgraf, Martin R. Sprick
Summary: Ovarian cancer, especially high-grade serous ovarian cancer (HGSOC), has the worst prognosis among all gynecological cancers. RAD51 expression is proposed as a biomarker of platinum resistance in HGSOC patients, which can help in selecting effective therapies for therapy-resistant patients.
EMBO MOLECULAR MEDICINE
(2021)
Review
Oncology
Justin Fortune Creeden, Nisha S. Nanavaty, Katelyn R. Einloth, Cassidy E. Gillman, Laura Stanbery, Danae M. Hamouda, Lance Dworkin, John Nemunaitis
Summary: The text discussed the importance of homologous recombination and DNA repair for genome maintenance, as well as the impact of genetic variations in essential homologous recombination genes such as BRCA1 and BRCA2 on homologous recombination deficiency (HRD) and potential therapeutic strategies. It also highlighted the need for reliable HRD testing methods, as well as current treatment and research on synthetic lethality in HRD.
Review
Oncology
Pamela Soberanis Pina, Stephanie Lheureux
Summary: Ovarian cancer is a highly lethal tumor in women, often diagnosed at advanced stages. Current standard of care includes surgery and chemotherapy, but relapse is common. Recently, PARP inhibitors have been used in the treatment of high-grade ovarian cancer with DNA repair defects. However, resistance to PARP inhibitors is a major challenge, and research is focused on finding agents to re-sensitize tumor cells and overcome or bypass resistance.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Oncology
Tingting Chen, Tong Yu, Shuping Zhuang, Yiding Geng, Junwen Xue, Jiayi Wang, Liqiang Ai, Bo Chen, Zhangxiang Zhao, Yawei Li, Jinghao Wang, Haihai Liang, Yan Xu, Yunyan Gu
Summary: This study developed a qualitative signature for detecting BRCAness in OvCa and showed that patients classified as BRCAness had improved overall survival and progression-free survival, as well as increased sensitivity to immune checkpoint blockade.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Ionut-Gabriel Funingana, Marika A. Reinius, Angelica Petrillo, Joo Ern Ang, James D. Brenton
Summary: Epithelial ovarian carcinoma comprises distinct entities determining intrinsic sensitivity to platinum-based chemotherapy, with only a few biomarkers predicting treatment response. The recent integration of PARP inhibitors highlights the need for personalized ovarian cancer treatment based on tumor biology, emphasizing integrative strategies for future personalized medicine programs and composite biomarkers.
SEMINARS IN CANCER BIOLOGY
(2021)
Review
Oncology
Rachel Royfman, Emma Whiteley, Olivia Noe, Susan Morand, Justin Creeden, Laura Stanbery, Danae Hamouda, John Nemunaitis
Summary: Mutations in BRCA1 or BRCA2 genes increase the risk of breast and ovarian cancer by impacting DNA repair and homologous recombination. Dysregulation of BRCA1/2 not only drives oncogenesis and cancer proliferation, but also affects immune response, influencing disease progression.
Review
Oncology
Renata Colombo Bonadio, Maria del Pilar Estevez-Diz
Summary: PARP inhibitors have become an important treatment option for ovarian cancer, with varying benefits depending on the homologous recombination status, particularly in patients with BRCA mutations or HRD tumors. Strategies to overcome resistance and enhance effectiveness in HRP tumors are being explored through various combination therapies, including those with antiangiogenics and immunotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yong Wu, Siyu Chen, Yang Shao, Ying Su, Qin Li, Jiangchun Wu, Jun Zhu, Hao Wen, Yan Huang, Zhong Zheng, Xiaojun Chen, Xingzhu Ju, Shenglin Huang, Xiaohua Wu, Zhixiang Hu
Summary: This study identifies super-enhancer regulatory elements that are aberrantly activated in ovarian cancer (OC) and shows that they drive the expression of the transcription factor KLF5. KLF5 is associated with poor outcomes in OC patients and can promote tumor progression by enhancing the homologous recombination repair pathway and increasing PARP inhibitor resistance. The combination of SAHA and olaparib is found to significantly inhibit tumor growth and metastasis in PARP inhibitor-resistant OC cells with high KLF5 expression.
Article
Oncology
Hao Wen, Zheng Feng, Yutong Ma, Rui Liu, Qiuxiang Ou, Qinhao Guo, Yi Shen, Xue Wu, Yang Shao, Hua Bao, Xiaohua Wu
Summary: In this study, targeted next-generation sequencing was used to evaluate the role of HRD in predicting treatment efficacy and the associated genomic features in ovarian cancer patients. The findings suggest that HRD-positive status might serve as a predictive biomarker for platinum-based chemotherapy, and HRR gene mutations play a significant role in HRD beyond BRCA1/2 alterations.
Article
Oncology
Jeffrey A. How, Amir A. Jazaeri, Bryan Fellman, Molly S. Daniels, Suzanna Penn, Cara Solimeno, Ying Yuan, Kathleen Schmeler, Jerry S. Lanchbury, Kirsten Timms, Karen H. Lu, Melinda S. Yates
Summary: Understanding the molecular characteristics of ovarian cancer is crucial for individualizing treatment strategies. An HRD score of >=33 is associated with improved overall survival in ovarian cancer patients. Future studies should evaluate the potential benefits of using HRD score >=33 compared to the currently used threshold of >=42 for PARPi treatment.
Article
Oncology
Yue Han, Zhewei Guo, Lijuan Jiang, Xinyue Li, Jiahui Chen, Ling Ouyang, Yan Li, Xiaoying Wang
Summary: This study aimed to identify biomarkers of ovarian cancer, focusing on tumors with homologous recombination deficiency (HRD), to optimize immunotherapy. Using transcriptome data from the TCGA database, differentially expressed genes coding for CXCL10 and CCL5 were screened, and the results were validated using tissue sections. Single-cell sequencing data from the GEO database and TMB and SNP data from the TCGA database were used to determine the cellular origin of CXCL10 and CCL5. The expression levels of CXCL10 and CCL5 were correlated with HRD score, suggesting their potential as novel biomarkers for guiding immunotherapy in ovarian cancer.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Review
Oncology
Giuseppe Caruso, Federica Tomao, Gabriella Parma, Mariateresa Lapresa, Francesco Multinu, Innocenza Palaia, Giovanni Aletti, Nicoletta Colombo
Summary: PARPi has become the standard of care in upfront treatment of advanced ovarian cancer, but there are still unresolved questions regarding maintenance therapy and the impact of PARPi on subsequent treatment needs to be studied.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Pharmacology & Pharmacy
Liliana Raimundo, Angela Paterna, Juliana Calheiros, Joana Ribeiro, David S. P. Cardoso, Ilaria Piga, Susana Junqueira Neto, Denise Hegan, Peter M. Glazer, Stefano Indraccolo, Silva Mulhovo, Jose Luis Costa, Maria-Jose U. Ferreira, Lucilia Saraiva
Summary: The study demonstrates that BBIT20, a natural compound, inhibits homologous DNA repair in triple-negative breast and ovarian cancer cells, leading to DNA damage and apoptosis. BBIT20 shows significant antitumor activity in patient-derived cells and xenograft mouse models of ovarian cancer, with low toxicity in non-malignant cells and undetectable side effects in mice. Additionally, BBIT20 does not induce resistance and exhibits synergistic effects with cisplatin and olaparib in 2D and 3D models of these cancer cells.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sichun Zhou, Duo Li, Di Xiao, Tianyu Wu, Xin Hu, Yu Zhang, Jun Deng, Jing Long, Simeng Xu, Jingtao Wu, Gaofeng Li, Mei Peng, Xiaoping Yang
Summary: This study identified that downregulation of PKM2 is a novel therapeutic strategy to enhance the effectiveness of Ola in treating ovarian cancer. Silencing PKM2 or using small molecular inhibitor Shikonin can enhance the therapeutic effect of Ola on ovarian cancer cells and reduce cell growth, migration, and induce apoptosis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Oncology
Simone N. Koole, Philip C. Schouten, Jan Hauke, Roel J. C. Kluin, Petra Nederlof, Lisa K. Richters, Gabriele Krebsbach, Karolina Sikorska, Maartje Alkemade, Mark Opdam, Jules H. Schagen van Leeuwen, Henk W. R. Schreuder, Ralph H. M. Hermans, Ignace H. J. T. de Hingh, Constantijne H. Mom, Henriette J. G. Arts, Maaike van Ham, Peter van Dam, Peter Vuylsteke, Joyce Sanders, Hugo M. Horlings, Koen K. van de Vijver, Eric Hahnen, Willemien J. van Driel, Rita Schmutzler, Gabe S. Sonke, Sabine C. Linn
Summary: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin to interval cytoreductive surgery improves recurrence-free and overall survival in patients with stage III ovarian cancer. HRD ovarian tumors, especially HRD/BRCAwt and non-HRD/BRCAwt tumors, respond best to treatment with HIPEC.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Review
Genetics & Heredity
Kateryna Kratzer, Landon J. Getz, Thibaut Peterlini, Jean-Yves Masson, Graham Dellaire
Summary: Gene therapy for genetic diseases has gained increased attention, but faces technical challenges and ethical barriers. Current research is primarily focused on improving gene therapy and gene editing techniques, with less emphasis on the timing and rationale for using such technology.
Article
Biochemistry & Molecular Biology
Ayeong So, Elodie Dardillac, Ali Muhammad, Catherine Chailleux, Laura Sesma-Sanz, Sandrine Ragu, Eric Le Cam, Yvan Canitrot, Jean Yves Masson, Pauline Dupaigne, Bernard S. Lopez, Josee Guirouilh-Barbat
Summary: Selection of DSB repair pathway is crucial for genetic stability. RAD51 plays a role in preventing nonconservative repair by controlling the second step of the repair process in human cells. RAD51's DNA binding ability is required for inhibiting SSA/A-EJ, not GC.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Larissa Milano, Clara F. Charlier, Rafaela Andreguetti, Thomas Cox, Eleanor Healing, Marcos P. Thome, Ruan M. Elliott, Leona D. Samson, Jean-Yves Masson, Guido Lenz, Joao Antonio P. Henriques, Axel Nohturfft, Lisiane B. Meira
Summary: The study investigates the effects of the alkylating agent MMS on gene expression in mouse liver using mice deficient in the enzyme Aag. It shows that Aag deficiency leads to a reduction in the cellular stress response induced by alkylation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Meshach Asare-Werehene, Hideaki Tsuyoshi, Huilin Zhang, Reza Salehi, Chia-Yu Chang, Euridice Carmona, Clifford L. Librach, Anne-Marie Mes-Masson, Chia-Ching Chang, Dylan Burger, Yoshio Yoshida, Benjamin K. Tsang
Summary: Ovarian cancer is a deadly disease primarily due to late diagnosis, recurrence, and chemoresistance. This study demonstrates that the over-expression of plasma gelsolin (pGSN) downregulates the anti-tumor functions of M1 macrophages, leading to chemoresistance and poor patient survival. Understanding the immunological role of pGSN in the tumor microenvironment can help improve the effectiveness of immunotherapy for ovarian cancer patients.
Review
Genetics & Heredity
Elias B. Habib, Sabateeshan Mathavarajah, Graham Dellaire
Summary: Pre-mRNA processing factor 4 kinase (PRP4K) is a conserved kinase that plays important roles in spliceosomal assembly. However, recent studies have revealed that PRP4K is also involved in various cellular pathways, including transcription regulation, spindle assembly checkpoint, and tumor suppression, contributing to tumorigenesis and chemotherapy response.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
Charles Dariane, Sylvie Clairefond, Benjamin Peant, Laudine Communal, Zhe Thian, Veronique Ouellet, Dominique Trudel, Nazim Benzerdjeb, Feryel Azzi, Arnaud Mejean, Marc-Olivier Timsit, Manon Baures, Jacques-Emmanuel Guidotti, Vincent Goffin, Pierre I. Karakiewicz, Anne-Marie Mes-Masson, Fred Saad
Summary: Keratin-7 overexpression is associated with poor prognosis in several cancers, and its high expression in benign glands surrounding localized prostate tumors is correlated with shorter bone metastasis-free survival and increased risk of cancer-specific mortality. In prostate cancer patients, high Keratin-7 expression is significantly associated with hypertrophic basal cell phenotype.
Article
Oncology
Maxime Cahuzac, Benjamin Peant, Anne-Marie Mes-Masson, Fred Saad
Summary: This study established new models of resistance in prostate cancer cells and identified potential targets, such as DNA repair, autophagy, and ROCK2, to reverse acquired olaparib-resistance.
Article
Biology
Marjorie Fournier, Amelie Rodrigue, Larissa Milano, Jean-Yves Bleuyard, Anthony M. Couturier, Jacob Wall, Jessica Ellins, Svenja Hester, Stephen J. Smerdon, Laszlo Tora, Jean-Yves Masson, Fumiko Esashi
Summary: The tumour suppressor PALB2 stimulates homologous recombination (HR) repair of DNA damage and protects active genes during DNA replication. Acetylation of the 7K-patch within the PALB2 chromatin association motif (ChAM) by KAT2A/2B enhances PALB2's association with nucleosomes. DNA damage triggers deacetylation of ChAM and increases PALB2's mobility. Mutations in the 7K-patch affect PALB2's chromatin binding, leading to defects in RAD51 foci formation and decreased cell survival.
Article
Biochemistry & Molecular Biology
Tharindu L. Suraweera, J. P. Jose Merlin, Graham Dellaire, Zhaolin Xu, H. P. Vasantha Rupasinghe
Summary: Cancer is a leading cause of death globally, but current treatments like chemotherapy and radiation therapy have significant side effects. Therefore, the prevention of cancer through dietary modifications has gained interest. This study examined the potential of selected flavonoids in reducing reactive oxygen species (ROS) and DNA damage induced by carcinogens through the activation of the Nrf2/ARE pathway. The results showed that genistein and PCB2 could effectively reduce ROS and DNA damage, and further research is needed to understand the role of dietary flavonoids in regulating the Nrf2/ARE pathway in carcinogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Ludivine C. Litzler, Astrid Zahn, Kiersten L. Dionne, Adrien Sprumont, Silvana R. Ferreira, Michael R. F. Slattery, Stephen P. Methot, Anne-Marie Patenaude, Steven Hebert, Nisha Kabir, Poorani Ganesh Subramani, Seolkyoung Jung, Stephane Richard, Claudia L. Kleinman, Javier M. Di Noia
Summary: Protein arginine methyltransferase 1 (PRMT1) is upregulated via Myc and mTORC1 during positive selection and plays a critical role in transcription. Deleting Prmt1 compromises antibody affinity maturation by hampering proliferation and cycling of GCBC. Moreover, Prmt1 restricts plasma cell differentiation and this function is co-opted by B cell lymphoma cells.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Doris Plecas, Nikol Mraz, Anne Marie Patanaude, Tea Pribic, Ivana Pavlinac Dodig, Renata Pecotic, Gordan Lauc, Ozren Polasek, Zoran Dogas
Summary: This study aimed to investigate the potential use of N-glycome as a biomarker for severe obstructive sleep apnea (OSA). By comparing 70 subjects with AHI over 30 to 23 controls with AHI under 5, significant associations were found between three plasma glycan peaks, one IgG glycan peak, and severe OSA. Additionally, patients with severe OSA showed accelerated biological aging. In conclusion, plasma N-glycome can serve as a biomarker for severe OSA.
Article
Biochemistry & Molecular Biology
Sabateeshan Mathavarajah, Graham Dellaire
Summary: The cGAS-STING pathway integrates DNA damage and cellular stress with type I interferon signaling, and the dysregulation of this pathway is associated with various diseases. L1 retroelements play a crucial role in the induction of cGAS-STING and interferon signaling. TREX1 is an important suppressor of cGAS-STING and L1 activity, and its loss leads to the accumulation of L1 retroelements.
BIOCHEMISTRY AND CELL BIOLOGY
(2023)
Article
Evolutionary Biology
Sabateeshan Mathavarajah, Andrew W. Thompson, Matthew R. Stoyek, T. Alexander Quinn, Stephane Roy, Ingo Braasch, Graham Dellaire
Summary: This study reveals that aquatic vertebrates undergo transcriptional rewiring of innate immune signaling pathways during limb and fin regeneration to promote immune cell recruitment. The study also shows that cGAS-STING pathway and various suppressors of cytosolic DNA play important roles in the regeneration process. The findings provide insights into the molecular mechanisms behind tissue regeneration in aquatic animals.
JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION
(2023)
Article
Biochemistry & Molecular Biology
Abdul B. Hayran, Nina B. Liabakk, Per A. Aas, Anna Kusnierczyk, Cathrine B. Vagbo, Antonio Sarno, Tobias S. Iveland, Konika Chawla, Astrid Zahn, Javier M. Di Noia, Geir Slupphaug, Bodil Kavli
Summary: Activation-induced cytidine deaminase (AID) interacts with replication protein A (RPA) to promote conversion of cytosine to uracil in immunoglobulin (Ig) genes. Uracil-DNA glycosylase (UNG) plays a crucial role in Ig diversification and genome repair through its interaction with AID. The study shows that the UNG:RPA interaction is important for class switch recombination (CSR) and repair of AID-induced uracil, but has no significant impact on total genomic uracil levels.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Wojciech Kluzniak, Agata Szymiczek, Amelie Rodrigue, Dominika Wokolorczyk, Bogna Rusak, Klaudia Stempa, Tomasz Huzarski, Jacek Gronwald, Jan Lubinski, Neda Zamani, Shiyu Zhang, Jean-Yves Masson, Steven A. Narod, Cezary Cybulski, Mohammad R. Akbari
Summary: In the Polish population, the low-penetrance BRCA2 p.K3326* variant is associated with increased breast cancer risk only in individuals homozygous for the T allele of the ALDH2 rs10744777 variant, suggesting an interaction between these two variants.
JCO PRECISION ONCOLOGY
(2022)