Article
Biochemistry & Molecular Biology
Kristie-Ann Dickson, Tao Xie, Christian Evenhuis, Yue Ma, Deborah J. Marsh
Summary: PARP inhibitors have shown efficacy in treating tumors with BRCA gene defects, improving survival outcomes. Variability exists between different PARP inhibitors in terms of chemical structure, toxicity, and cell survival, with acquired resistance being a concerning issue that needs further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mariana Paes Dias, Vivek Tripathi, Ingrid van der Heijden, Ke Cong, Eleni-Maria Manolika, Jinhyuk Bhin, Ewa Gogola, Panagiotis Galanos, Stefano Annunziato, Cor Lieftink, Miguel Andujar-Sanchez, Sanjiban Chakrabarty, Graeme C. M. Smith, Marieke van de Ven, Roderick L. Beijersbergen, Jirina Bartkova, Sven Rottenberg, Sharon Cantor, Jiri Bartek, Arnab Ray Chaudhuri, Jos Jonkers
Summary: A study reveals that loss of LIG3 enhances the toxicity of PARP inhibitors in BRCA1-deficient cancer, potentially serving as a therapeutic target.
Review
Oncology
Maria Clara Saad Menezes, Farah Raheem, Lida Mina, Brenda Ernst, Felipe Batalini
Summary: PARP inhibitors are effective against breast cancers with mutations in DNA repair genes, especially BRCA1 and BRCA2. Olaparib and talazoparib are two FDA-approved PARPi for breast cancer treatment. In addition to inherited BRCA mutations, PARPi have broader indications for patients with other cancer types (such as prostate and ovarian cancer).
Editorial Material
Health Care Sciences & Services
Laura Cortesi, Claudia Piombino, Angela Toss
Summary: This article explores the role of germline mutations in HRR-related genes other than BRCA1/2 in predicting responses to treatment and prognosis in breast and pancreatic cancer. Mutations in PALB2 and ATM genes have shown potential as predictive factors for treatment response and prognosis, suggesting their inclusion in routine sequencing for biological characterization of these cancers.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Cell Biology
Lin Dong, Tingting Wang, Ning Li, Hongwen Yao, Jianming Ying, Lingying Wu, Guangwen Yuan
Summary: This study found that HRR gene mutations are highly prevalent in USC and may serve as a prognostic marker for better clinical outcomes. Further research is needed to determine if tHRRmt patients can benefit from treatments targeting homologous recombination.
Article
Oncology
Olga T. Filippova, Pier Selenica, Fresia Pareja, Mahsa Vahdatinia, Yingjie Zhu, Xin Pei, Nadeem Riaz, Kara Long Roche, Dennis S. Chi, Nadeem R. Abu-Rustum, Lora H. Ellenson, Jorge S. Reis-Filho, Dmitriy Zamarin, Britta Weigelt
Summary: Younger HGSOC patients more frequently carry pathogenic BRCA1 germline mutations and genomic features of HRD, while older patients preferentially display aging-related mutational signatures, fewer pathogenic BRCA1 germline mutations and genomic features of HRD.
GYNECOLOGIC ONCOLOGY
(2021)
Review
Gastroenterology & Hepatology
Cha Len Lee, Spring Holter, Ayelet Borgida, Anna Dodd, Stephanie Ramotar, Robert Grant, Kristy Wasson, Elena Elimova, Raymond W. Jang, Malcolm Moore, Tae Kyoung Kim, Korosh Khalili, Carol-Anne Moulton, Steven Gallinger, Grainne M. O'Kane, Jennifer J. Knox
Summary: The presence of germline BRCA2 likely pathogenic variant has significant impact on treatment decisions for PACC patients, highlighting the importance of genomic testing in personalized treatment. Our case series provides practical evidence for the value of germline and somatic profiling in managing rare diseases like PACC.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Cell Biology
Jinhyuk Bhin, Mariana Paes Dias, Ewa Gogola, Frank Rolfs, Sander R. Piersma, Roebi de Bruijn, Julian R. de Ruiter, Bram van den Broek, Alexandra A. Duarte, Wendy Sol, Ingrid van der Heijden, Christina Andronikou, Taina S. Kaiponen, Lara Bakker, Cor Lieftink, Ben Morris, Roderick L. Beijersbergen, Marieke van de Ven, Connie R. Jimenez, Lodewyk F. A. Wessels, Sven Rottenberg, Jos Jonkers
Summary: BRCA1 and BRCA2 are involved in homologous recombination repair, and BRCA1/2-deficient cancers are sensitive to PARP inhibitors but eventually develop resistance. Restoration of HR is observed in 62% of PARPi-resistant BRCA1-deficient tumors but not in BRCA2-deficient tumors. 53BP1 loss is the prevalent resistance mechanism in HR-proficient BRCA1-deficient tumors, while PARG loss is mainly induced in BRCA2-deficient tumors. Additionally, multi-omics analysis identifies potential genes and pathways involved in modulating PARP inhibitor response.
Article
Reproductive Biology
A. W. Adamson, Y. C. Ding, L. Steele, L. A. Leong, R. Morgan, M. T. Wakabayashi, E. S. Han, T. H. Dellinger, P. S. Lin, A. A. Hakim, S. Wilczynski, C. D. Warden, S. Tao, V. Bedell, M. C. Cristea, S. L. Neuhausen
Summary: This study investigated genetic alterations in high-grade serous ovarian cancers (HGSCs) and found that about one-third of tumors had genetic variants associated with DNA damage and PI3K/AKT/mTOR pathways. These variants were associated with relapse-free and overall survival.
JOURNAL OF OVARIAN RESEARCH
(2023)
Article
Oncology
Nicola Bassi, Henrikke Nilsen Hovland, Kashif Rasheed, Elisabeth Jarhelle, Nikara Pedersen, Eunice Kabanyana Mchaina, Sara Marie Engelsvold Bakkan, Nina Iversen, Hildegunn Hoberg-Vetti, Bjorn Ivar Haukanes, Per Morten Knappskog, Ingvild Aukrust, Elisabet Ognedal, Marijke Van Ghelue
Summary: This study investigated the effects of 11 rare BRCA1 missense variants on DNA repair and gene expression. The majority of the variants showed reduced functionality, highlighting the importance of accurately classifying these variants.
Article
Oncology
Na Li, Magnus Zethoven, Simone McInerny, Lisa Devereux, Yu-Kuan Huang, Niko Thio, Dane Cheasley, Sara Gutierrez-Enriquez, Alejandro Moles-Fernandez, Orland Diez, Tu Nguyen-Dumont, Melissa C. Southey, John L. Hopper, Jacques Simard, Martine Dumont, Penny Soucy, Alfons Meindl, Rita Schmutzler, Marjanka K. Schmidt, Muriel A. Adank, Irene L. Andrulis, Eric Hahnen, Christoph Engel, Fabienne Lesueur, Elodie Girard, Susan L. Neuhausen, Elad Ziv, Jamie Allen, Douglas F. Easton, Rodney J. Scott, Kylie L. Gorringe, Paul A. James, Ian G. Campbell
Summary: Bi-allelic loss-of-function (LoF) variants in the NTHL1 gene are associated with a high-risk hereditary multi-tumor syndrome, including breast cancer. Heterozygous variants in NTHL1 may contribute to hereditary breast cancer, with an increased risk associated with missense variants. The study suggests that pathogenic germline coding variants in NTHL1 are linked to a low- to moderate-risk of breast cancer.
Review
Oncology
Chao Yin, Monika Kulasekaran, Tina Roy, Brennan Decker, Sonja Alexander, Mathew Margolis, Reena C. Jha, Gary M. Kupfer, Aiwu R. He
Summary: Biliary tract cancers are rare but deadly gastrointestinal tumors that are often diagnosed at advanced stages. Chemotherapies have limited effectiveness, so there is a need for new treatments. This review explores the use of PARP inhibitors in treating biliary tract cancers and discusses expanding patient eligibility and the potential use of reliable HRD surrogate markers.
Article
Biology
Ilirjana Bajrami, Callum Walker, Dragomir B. Krastev, Daniel Weekes, Feifei Song, Andrew J. Wicks, John Alexander, Syed Haider, Rachel Brough, Stephen J. Pettitt, Andrew N. J. Tutt, Christopher J. Lord
Summary: The study investigated the synthetic lethality between BRCA gene defects and inhibition of two sirtuin genes, SIRT1 or SIRT6, which was associated with replication stress and increased PARylation. The authors demonstrated that this synthetic lethality could be reversed by genetic ablation of PARP1 or HPF1.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Andrey Kechin, Ulyana Boyarskikh, Alexey Barinov, Alexander Tanas, Svetlana Kazakova, Anastasia Zhevlova, Evgeniy Khrapov, Sergey Subbotin, Olga Mishukova, Tatiana Kekeeva, Irina Demidova, Maxim Filipenko
Summary: This study investigates the distribution of BRCA1/2 pathogenic variants in Russian ovarian cancer patients. The most common variant identified was c.5266dup, followed by c.4035del, c.1961del, c.181 T > G, and others. The study also suggests that the c.5286 T > G variant in BRCA2 is a new founder mutation that occurred approximately 700 years ago.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Review
Biochemistry & Molecular Biology
Xianzhe Yu, Lingling Zhu, Ting Wang, Lu Li, Jiewei Liu, Guowei Che, Qinghua Zhou
Summary: The efficacy of anti-cancer therapies is hindered by DNA damage-response mechanisms that repair DNA damage and result in treatment resistance. DNA damage repair inhibitors (DDRis), particularly polyadenosine diphosphate ribose polymerase inhibitors, show promise in overcoming therapeutic resistance. Combination therapies involving DDRis have the potential to improve outcomes for solid tumors.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)