Article
Oncology
Caiyu Sun, Weiqiang Jing, Gaozhong Xiong, Dapeng Ma, Yueke Lin, Xiaoting Lv, Yunxue Zhao, Xiaomin Ma, Lihui Zhu, Xuecheng Shen, Min Yang, Zhenzhi Qin, Yeping Cheng, Haocheng Xuan, Tao Li, Lihui Han
Summary: This study identified Src and PARP1 as novel synthetic lethal partners, and the combination therapy showed significant anti-tumor effects without causing obvious side effects. The findings suggest that targeting both PARP1 and Src may broaden the strategies for HCC treatment and benefit patients with high Src activation and resistance to PARP1 inhibitors alone.
Article
Chemistry, Medicinal
Tomohiro Asai, Masafumi Yokota, Hideki Isomura, Hiroyuki Koide, Naoyuki Sakurai, Ayaka Okamoto, Hidenori Ando, Takehisa Dewa, Naoto Oku
Summary: This study explores the synthetic lethal interaction between PTEN loss and PARP1 gene silencing in human triple-negative breast cancer cells. The delivery of siPARP1 using polycation liposomes resulted in cytotoxicity in PTEN-null MDA-MB-468 cells, but not in PTEN-positive MDA-MB-231 cells or normal cells. Simultaneous knockdown of PARP1 and PTEN inhibited cell growth in MDA-MB-231 cells. Furthermore, PARP1 knockdown led to increased DNA breaks and apoptosis in MDA-MB-468 cells compared to MDA-MB-231 cells. These findings suggest that synthetic lethality via PARP1 gene silencing holds promise for the treatment of PTEN-null breast cancer.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Medicine, Research & Experimental
Chen Yang, Yuchen Guo, Ruolan Qian, Yiwen Huang, Linmeng Zhang, Jun Wang, Xiaowen Huang, Zhicheng Liu, Wenxin Qin, Cun Wang, Huimin Chen, Xuhui Ma, Dayong Zhang
Summary: Through the analysis of synthetic lethality interactions, potential therapeutic targets in liver cancer were identified, suggesting a novel personalized treatment approach. This may offer more effective treatment options for patients with liver cancer.
Review
Biochemistry & Molecular Biology
Hannah E. Neiger, Emily L. Siegler, Yihui Shi
Summary: BRCA1 and BRCA2 are tumor suppressor genes crucial in DNA repair mechanisms. Synthetic lethality, caused by simultaneous perturbations of two genes, can help identify new therapeutic options for BRCA1/2 mutations. PARP inhibitor Olaparib has shown success as the first synthetic lethality-based therapy for BRCA1/2 breast and ovarian cancer, but drug resistance poses a challenge for targeted cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Pan Juncheng, Adrien Joseph, Antoine Lafarge, Isabelle Martins, Florine Obrist, Jonathan Pol, Ester Saavedra, Sijing Li, Allan Sauvat, Giulia Cerrato, Sarah Levesque, Marion Leduc, Oliver Kepp, Sylvere Durand, Fanny Aprahamian, Nitharsshini Nirmalathansan, Judith Michels, Guido Kroemer, Maria Castedo
Summary: This study found that high activity of PARP1 in non-small cell lung cancer cells affects the tumor microenvironment, leading to compromised immunosurveillance and reduced infiltration of cytotoxic T lymphocytes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Ananna Bhadra Arna, Hardikkumar Patel, Ravi Shankar Singh, Frederick S. Vizeacoumar, Anthony Kusalik, Andrew Freywald, Franco J. Vizeacoumar, Yuliang Wu
Summary: DEAD/H-box helicases play important roles in various aspects of RNA metabolism and their dysregulation is associated with cancer. Synthetic lethality (SL) and synthetic dosage lethality (SDL) approaches, which exploit genetic interactions among cancer-related genes, have shown promise in cancer research. This review analyzes the gene expression of DEAD/H-box helicases in different cancer types and discusses the potential therapeutic applications of their SL/SDL interactions. The latest developments in clinical applications and challenges in targeting DEAD/H-box helicases for drug discovery are also discussed.
FRONTIERS IN ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Xiaopeng Peng, Wanyi Pan, Feng Jiang, Weiming Chen, Zetao Qi, Weijie Peng, Jianjun Chen
Summary: This review provides an overview of recent progress in PARP1-based drug discovery, focusing on PARP1 inhibitor-based combination therapy and other PARP1-targeting strategies. Co-crystal structures and binding interactions between PARP1 inhibitors and their target proteins are summarized. The challenges and future directions for PARP-based drug discovery in cancer therapy are also discussed in detail.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Oncology
Colm J. Ryan, Ishan Mehta, Narod Kebabci, David J. Adams
Summary: Synthetic lethal interactions, especially between paralogs, can be exploited for cancer targeted therapeutics development and existing small-molecule drugs may also target multiple paralogs simultaneously. The identification of these interactions is crucial for drug development.
Article
Oncology
Joseph S. Baxter, Rachel Brough, Dragomir B. Krastev, Feifei Song, Sandhya Sridhar, Aditi Gulati, John Alexander, Theodoros I. Roumeliotis, Zuza Kozik, Jyoti S. Choudhary, Syed Haider, Stephen J. Pettitt, Andrew N. J. Tutt, Christopher J. Lord
Summary: The synthetic lethal effects of FBXW7 have been identified, which could serve as a starting point for further drug discovery and development in this area.
MOLECULAR ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Biyu Zhang, Chen Tang, Yanli Yao, Xiaohan Chen, Chi Zhou, Zhiting Wei, Feiyang Xing, Lan Chen, Xiang Cai, Zhiyuan Zhang, Shuyang Sun, Qi Liu
Summary: Synthetic lethality is becoming an important cancer therapeutic paradigm, but comprehensive selective treatment opportunities for various tumors have not been fully explored. The Synthetic Lethality Knowledge Graph (SLKG) integrates data on different tumors, drugs, and drug targets to provide therapy options for synthetic lethality and synthetic dosage lethality, prioritizing the identification of repurposable drug candidates and combinations with supporting evidence for novel tumor therapy discovery.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Thorsten Mosler, H. Irem Baymaz, Justus F. Graef, Ivan Mikicic, Georges Blattner, Edward Bartlett, Matthias Ostermaier, Rossana Piccinno, Jiwen Yang, Andrea Voigt, Marco Gatti, Stefania Pellegrino, Matthias Altmeyer, Katja Luck, Ivan Ahel, Vassilis Roukos, Petra Beli
Summary: TPX2 is a direct binding protein of PARP1, regulating its ADP-ribosylation activity. High TPX2 expression levels are associated with sensitivity of BRCA1/2-mutated cancers to PARP inhibitors.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Tao Zhu, Ju-Yan Zheng, Ling-Ling Huang, Yan-Hong Wang, Di-Fei Yao, Hai-Bin Dai
Summary: Poly (ADP-ribose) polymerase 1 (PARP1) is a crucial sensor for DNA damage repair but resistance to PARP inhibitors (PARPi) is a common issue in cancer treatment. This review focuses on the identification of novel substrates and regulators of PARP1-catalyzed PARylation, aiming to present potential therapeutic interventions that can overcome resistance to PARPi.
FRONTIERS IN PHARMACOLOGY
(2023)
Editorial Material
Oncology
Pan Juncheng, Antoine Lafarge, Guido Kroemer, Maria Castedo
Summary: High levels of intracellular PAR resulting from elevated PARP1 activity correlate with poor infiltration of non-small cell lung cancers by cytotoxic T lymphocytes and dismal patient prognosis. Preclinical experimentation demonstrates that inhibiting PARP1 in cancer cells has strong immunostimulatory effects.
Article
Oncology
Leo Yamada, Motonobu Saito, Aung Kyi Thar Min, Katsuharu Saito, Mai Ashizawa, Koji Kase, Shotaro Nakajima, Hisashi Onozawa, Hirokazu Okayama, Hisahito Endo, Shotaro Fujita, Wataru Sakamoto, Zenichiro Saze, Tomoyuki Momma, Kosaku Mimura, Shinji Ohki, Koji Kono
Summary: EZH2 inhibitors show selective sensitivity against ARID1A-deficient GC cells, potentially affecting cell survival and proliferation by modulating the PI3K/AKT signaling pathway. This suggests the potential efficacy of targeted therapy using EZH2 inhibitors in ARID1A-deficient GC.
Review
Oncology
Laia Castells-Roca, Eudald Tejero, Benjamin Rodriguez-Santiago, Jordi Surralles
Summary: The concept of synthetic lethality (SL) has played a crucial role in cancer treatment, with CRISPR technology being widely used to discover new genetic interactions. Combining therapies based on SL interactions have the potential to reduce toxicity and improve efficacy in cancer treatment.
Article
Genetics & Heredity
Mei-Shiue Kuo, Julien Adam, Nicolas Dorvault, Angelique Robin, Luc Friboulet, Jean-Charles Soria, Ken A. Olaussen
Article
Oncology
Siddhartha Devarakonda, Federico Rotolo, Ming-Sound Tsao, Irena Lanc, Elisabeth Brambilla, Ashiq Masood, Ken A. Olaussen, Robert Fulton, Shingo Sakashita, Anne McLeer-Florin, Keyue Ding, Gwenael Le Teuff, Frances A. Shepherd, Jean-Pierre Pignon, Stephen L. Graziano, Robert Kratzke, Jean-Charles Soria, Lesley Seymour, Ramaswamy Govindan, Stefan Michiels
JOURNAL OF CLINICAL ONCOLOGY
(2018)
Article
Oncology
Leonie Ferrer, Matteo Giaj Levra, Marie Brevet, Martine Antoine, Julien Mazieres, Giulio Rossi, Rita Chiari, Virginie Westeel, Michel Poudenx, Jacques Letreut, Radj Gervais, Giorgia Osman, Nicolas Girard, Anne Claire Toffart, Silvia Novello, Denis Moro-Sibilot
JOURNAL OF THORACIC ONCOLOGY
(2019)
Review
Oncology
Gonzalo Recondo, Francesco Facchinetti, Ken A. Olaussen, Benjamin Besse, Luc Friboulet
NATURE REVIEWS CLINICAL ONCOLOGY
(2018)
Editorial Material
Oncology
Luc Friboulet, Jean-Charles Soria, Ken Andre Olaussen
CLINICAL CANCER RESEARCH
(2019)
Article
Oncology
Mickael Lattuca-Truc, Jean-Francois Timsit, Matteo Giaj Levra, Stephane Ruckly, Julie Villa, Isabelle Dumas, Julian Pinsolle, Leonie Ferrer, Pascale Guillem, Denis Moro-Sibilot, Anne-Claire Toffart
Review
Oncology
Niccolo Giaj-Levra, Matteo Giaj-Levra, Valerie Durieux, Silvia Novello, Benjamin Besse, Baktiar Hasan, Lizza E. Hendriks, Antonin Levy, Anne-Marie C. Dingemans, Thierry Berghmans
JOURNAL OF THORACIC ONCOLOGY
(2019)
Article
Respiratory System
C. Collart, D. Moro-Sibilot, M. Maignan, C. Schwebel, M. Giaj Levra, L. Ferrer, C. Paquier, D. Viglino, A-C Toffart
REVUE DES MALADIES RESPIRATOIRES
(2019)
Article
Oncology
Anne-Marie C. Dingemans, Lizza E. L. Hendriks, Thierry Berghmans, Antonin Levy, Baktiar Hasan, Corinne Faivre-Finn, Matteo Giaj-Levra, Niccolo Giaj-Levra, Nicolas Girard, Laurent Greillier, Sylvie Lantuejoul, John Edwards, Mary O'Brien, Martin Reck, Egbert F. Smit, Paul Van Schil, Pieter E. Postmus, Sara Ramella, Yolande Lievens, Mina Gaga, Nir Peled, Giorgio Scagliotti, Suresh Senan, Luiz Paz-Ares, Matthias Guckenberger, Fiona McDonald, Simon Ekman, Tanja Cufer, Hester Gietema, Maurizio Infante, Rafal Dziadziuszko, Solange Peters, Ramon Rami Porta, Johan Vansteenkiste, Christophe Dooms, Dirk de Ruysscher, Benjamin Besse, Silvia Novello
JOURNAL OF THORACIC ONCOLOGY
(2019)
Article
Oncology
Gonzalo Recondo, Laura Mezquita, Francesco Facchinetti, David Planchard, Anas Gazzah, Ludovic Bigot, Ahsan Z. Rizvi, Rosa L. Frias, Jean Paul Thiery, Jean-Yves Scoazec, Tony Sourisseau, Karen Howarth, Olivier Deas, Dariia Samofalova, Justine Galissant, Pauline Tesson, Floriane Braye, Charles Naltet, Pernelle Lavaud, Linda Mahjoubi, Aurelie Abou Lovergne, Gilles Vassal, Rastilav Bahleda, Antoine Hollebecque, Claudio Nicotra, Maud Ngo-Camus, Stefan Michiels, Ludovic Lacroix, Catherine Richon, Nathalie Auger, Thierry De Baere, Lambros Tselikas, Eric Solary, Eric Angevin, Alexander M. Eggermont, Fabrice Andre, Christophe Massard, Ken A. Olaussen, Jean-Charles Soria, Benjamin Besse, Luc Friboulet
CLINICAL CANCER RESEARCH
(2020)
Review
Oncology
Francesco Facchinetti, Antoine Hollebecque, Rastislav Bahleda, Yohann Loriot, Ken A. Olaussen, Christophe Massard, Luc Friboulet
CLINICAL CANCER RESEARCH
(2020)
Article
Oncology
Francesco Facchinetti, Ludovic Lacroix, Laura Mezquita, Jean-Yves Scoazec, Yohann Loriot, Lambros Tselikas, Anas Gazzah, Etienne Rouleau, Julien Adam, Stefan Michiels, Christophe Massard, Fabrice Andre, Ken A. Olaussen, Gilles Vassal, Karen Howarth, Benjamin Besse, Jean-Charles Soria, Luc Friboulet, David Planchard
EUROPEAN JOURNAL OF CANCER
(2020)
Letter
Radiology, Nuclear Medicine & Medical Imaging
G. R. Ferretti, M. Giaj Levra, A. Jankowski, A. C. Toffart, D. Moro Sibilot
DIAGNOSTIC AND INTERVENTIONAL IMAGING
(2019)
Article
Oncology
Federico Rotolo, Chang-Qi Zhu, Elisabeth Brambilla, Stephen L. Graziano, Ken Olaussen, Thierry Le-Chevalier, Jean-Pierre Pignon, Robert Kratzke, Jean-Charles Soria, Frances A. Shepherd, Lesley Seymour, Stefan Michiels, Ming-Sound Tsao
TRANSLATIONAL LUNG CANCER RESEARCH
(2018)
Article
Oncology
Charlotte Leduc, Julien Adam, Emilie Louvet, Tony Sourisseau, Nicolas Dorvault, Marine Bernard, Elodie Maingot, Laura Faivre, Mei-Shiue Cassin-Kuo, Emilie Boissier, Marie-Charlotte Dessoliers, Angelique Robin, Odile Casiraghi, Caroline Even, Stephane Temam, Ken A. Olaussen, Jean-Charles Soria, Sophie Postel-Vinay