Review
Oncology
Chen Wang, Hui Fang, Jiawei Zhang, Ying Gu
Summary: Synthetic lethal screening is a promising method for identifying novel drug targets, particularly for targeting undruggable proteins like c-Myc. Inhibiting important functional nodes related to c-Myc in non-oncogene addicted networks may have catastrophic effects on tumor cells but not on normal cells. This research field has made progress in identifying these functional nodes and holds great potential for potent tumor treatment.
FRONTIERS OF MEDICINE
(2021)
Review
Medicine, Research & Experimental
Kevin J. Metcalf, Alaa Alazzeh, Zena Werb, Valerie M. Weaver
Summary: Treatment resistance leads to cancer patient mortality. Targeting mutational vulnerabilities with synthetic lethality has shown effectiveness in some cancers. The dialogue between tumor cells and the tumor microenvironment (TME) plays a crucial role in mediating resistance to cancer treatment. Expanding synthetic lethality to encompass contextual synthetic lethality has the potential to improve cancer therapy.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Chemistry, Medicinal
Victor M. M. Matias-Barrios, Xuesen Dong
Summary: DNA topoisomerase II (Top2) plays a crucial role in regulating DNA topology by generating temporary breaks, and cancer cells exploit enhanced Top2 functions for transcription and DNA replication during cell division. Inhibitors of Top2 are designed to trap it on DNA, causing cell cycle arrest and cell death. However, resistance to Top2 inhibitors can limit their efficacy, leading to the proposal of combination therapies targeting DNA damage repair machinery and oncogenic pathways for more effective tumor suppression.
Review
Pharmacology & Pharmacy
Kailin Li, Jieqiong You, Qian Wu, Wen Meng, Qiaojun He, Bo Yang, Chengliang Zhu, Ji Cao
Summary: Synthetic lethality is an effective antitumor strategy that has attracted great attention, with CDKs potentially serving as synthetic lethal factors when combined with certain oncogenes. This provides numerous antitumor treatment options and highlights the prospect of CDK inhibitors as antitumor compounds.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Oncology
Moein Ala
Summary: C-Myc overexpression in pancreatic cancer is associated with aggressive behavior of cancer cells and can regulate various cellular processes. Recent studies have shown that C-Myc can be targeted directly or indirectly, offering potential therapeutic strategies for pancreatic cancer.
CANCER BIOLOGY & THERAPY
(2022)
Review
Oncology
Giulio Donati, Bruno Amati
Summary: The MYC transcription factor plays a crucial role in tumor progression and therapeutic responses. Overexpression of MYC can lead to therapy resistance and create specific vulnerabilities in cancer cells that can be targeted by novel anticancer drugs.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Craig M. Goodwin, Andrew M. Waters, Jennifer E. Klomp, Sehrish Javaid, Kirsten L. Bryant, Clint A. Stalnecker, Kristina Drizyte-Miller, Bjoern Papke, Runying Yang, Amber M. Amparo, Irem Ozkan-Dagliyan, Elisa Baldelli, Valerie Calvert, Mariaelena Pierobon, Jessica A. Sorrentino, Andrew P. Beelen, Natalie Bublitz, Mareen Luethen, Kris C. Wood, Emanuel F. Petricoin III, Christine Sers, Autumn J. McRee, Adrienne D. Cox, Channing J. Der
Summary: Mutation of CDKN2A and activation of KRAS are crucial for the development and malignant growth of PDAC. Combination treatment with CDK4/6 and ERK-MAPK inhibitors synergistically suppresses the growth of PDAC cells and organoids by blocking compensatory upregulation of signaling pathways. CRISPR-Cas9 screening and protein activity mapping uncover novel combinations that enhance the potency of CDK4/6 inhibitors and overcome drug-induced compensations in PDAC.
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.
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
Federica Invrea, Simona Punzi, Consalvo Petti, Rosalba Minelli, Michael D. Peoples, Christopher A. Bristow, Valentina Vurchio, Alessia Corrado, Alberto Bragoni, Caterina Marchio, Andrea Bertotti, Livio Trusolino, Alberto Bardelli, Claudio Isella, Alessandro Carugo, Giulio F. Draetta, Enzo Medico
Summary: This study identified a promising therapeutic strategy for clinically aggressive CRC resistant to EGFR and BRAF-targeted treatments by combining the NEDD8 pathway inhibitor pevonedistat with EGFR pathway-targeted treatments, reversing compensatory feedback loops and inhibiting tumor growth and inducing apoptosis in preclinical models.
Article
Biotechnology & Applied Microbiology
Dexter Kai Hao Thng, Tan Boon Toh, Paolo Pigini, Lissa Hooi, Yock Young Dan, Pierce Kah-Hoe Chow, Glenn Kunnath Bonney, Masturah Bte Mohd Abdul Rashid, Ernesto Guccione, Dave Keng Boon Wee, Edward Kai-Hua Chow
Summary: In this study, we demonstrated that using splice-switch oligonucleotide (SSO) technologies and quadratic phenotypic optimization platform (QPOP) analysis, CHK1 and BRD4 were identified as effective synthetic lethal targets in MYC-deregulated hepatocellular carcinoma (HCC), suppressing HCC progression.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
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)
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
Gastroenterology & Hepatology
Tan Boon Toh, Jhin Jieh Lim, Lissa Hooi, Masturah Bte Mohd Abdul Rashid, Edward Kai-Hua Chow
JOURNAL OF HEPATOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Daniel Boon Loong Teh, Akshaya Bansal, Chou Chai, Tan Boon Toh, Robert Alan Jappy Tucker, Gil Gerald Lasam Gammad, Yanzhuang Yeo, Zhendong Lei, Xiang Zheng, Fengyuan Yang, John S. Ho, Nagarjun Bolem, Bing Cheng Wu, Muthu Kumar Gnanasammandhan, Lissa Hooi, Gavin Stewart Dawe, Camilo Libedinsky, Wei-Yi Ong, Barry Halliwell, Edward Kai-Hua Chow, Kah-Leong Lim, Yong Zhang, Brian K. Kennedy
ADVANCED MATERIALS
(2020)
Article
Oncology
Xi Yun Zhang, Deepa Rajagopalan, Tae-Hoon Chung, Lissa Hooi, Tan Boon Toh, Johann Shane Tian, Masturah Bte Mohd Abdul Rashid, Noor Rashidha Bte Meera Sahib, Mengjie Gu, Jhin Jieh Lim, Wilson Wang, Wee Joo Chng, Sudhakar Jha, Edward Kai-Hua Chow
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2020)
Article
Biotechnology & Applied Microbiology
Daryl Jin Tai Tay, Yangyang Song, Boya Peng, Tan Boon Toh, Lissa Hooi, Desiree-Faye Kaixin Toh, HuiQi Hong, Sze Jing Tang, Jian Han, Wei Liang Gan, Tim Hon Man Chan, Manchugondanahalli S. Krishna, Kiran M. Patil, Manikantha Maraswami, Teck Peng Loh, Yock Young Dan, Lei Zhou, Glenn Kunnath Bonney, Pierce Kah-Hoe Chow, Gang Chen, Edward Kai-Hua Chow, Minh T. N. Le, Leilei Chen
Summary: The study identified chemically modified antisense oligonucleotides (ASOs) targeting AZIN1 that effectively inhibited cancer cell viability in vitro and tumor growth in xenograft models, demonstrating the potential of AZIN1-targeting ASOs for a wide range of tumor types.
Article
Biochemical Research Methods
Tan Boon Toh, Zheng Liu, Hanry Yu, Eliza Li Shan Fong
Summary: This protocol successfully cultures HCC PDX cells into organoids with preserved viability, molecular features, and heterogeneity using a specific sponge scaffold.
Article
Multidisciplinary Sciences
Jeehyun Yoon, Oleg Grinchuk, Srinivasaraghavan Kannan, Melgious Jin Yan Ang, Zhenglin Li, Emmy Xue Yun Tay, Ker Zhing Lok, Bernice Woon Li Lee, You Heng Chuah, Kimberly Chia, Roberto Tirado Magallanes, Chenfei Liu, Haonan Zhao, Jin Hui Hor, Jhin Jieh Lim, Touati Benoukraf, Tan Boon Toh, Edward Kai-Hua Chow, Jean-Paul Kovalik, Jianhong Ching, Shi-Yan Ng, Ming Joo Koh, Xiaogang Liu, Chandra Shekhar Verma, Derrick Sek Tong Ong
Summary: The study reveals the dependency of GBM on biotin distribution, suggesting that rational cotargeting of biotin-dependent metabolism and epigenetic pathways may be explored for GSC eradication.
Article
Engineering, Biomedical
Joanne Tze Chin Lim, Leng Gek Kwang, Nicholas Ching Wei Ho, Clarissa Chin Min Toh, Nathaniel Sheng Hua Too, Lissa Hooi, Touati Benoukraf, Pierce Kah-Hoe Chow, Yock Young Dan, Edward Kai-Hua Chow, Tan Boon Toh, Eliza Li Shan Fong
Summary: Hepatocellular carcinoma (HCC) is a common and deadly form of cancer. Despite advancements in treatment, the impact of anti-angiogenic therapies on overall survival of HCC patients is limited. This study demonstrates that endothelial cells have roles beyond angiogenesis in supporting tumor progression and generating an inflammatory microenvironment. These findings highlight the importance of understanding the interplay between angiogenesis and the immune milieu in HCC.
Article
Oncology
Jhin Jieh Lim, Lissa Hooi, Yock Young Dan, Glenn K. Bonney, Lei Zhou, Pierce K. -H. Chow, Cheng Ean Chee, Tan Boon Toh, Edward K. -H. Chow
Summary: This study proposes rational drug combination design and validation in patient-derived HCC avatar models to improve the therapeutic potential of proteasome and CDK inhibitors, representing a feasible approach towards developing more clinically relevant treatment strategies for HCC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Dexter Kai Hao Thng, Tan Boon Toh, Paolo Pigini, Lissa Hooi, Yock Young Dan, Pierce Kah-Hoe Chow, Glenn Kunnath Bonney, Masturah Bte Mohd Abdul Rashid, Ernesto Guccione, Dave Keng Boon Wee, Edward Kai-Hua Chow
Summary: In this study, we demonstrated that using splice-switch oligonucleotide (SSO) technologies and quadratic phenotypic optimization platform (QPOP) analysis, CHK1 and BRD4 were identified as effective synthetic lethal targets in MYC-deregulated hepatocellular carcinoma (HCC), suppressing HCC progression.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Dexter Kai Hao Thng, Lissa Hooi, Clarissa Chin Min Toh, Jhin Jieh Lim, Deepa Rajagopalan, Imran Qamar Charles Syariff, Zher Min Tan, Masturah Bte Mohd Abdul Rashid, Lei Zhou, Alfred Wei Chieh Kow, Glenn Kunnath Bonney, Brian Kim Poh Goh, Juinn Huar Kam, Sudhakar Jha, Yock Young Dan, Pierce Kah Hoe Chow, Tan Boon Toh, Edward Kai-Hua Chow
Summary: Hepatocellular carcinoma (HCC) is a highly lethal cancer with high prevalence worldwide. In this study, we demonstrated the overexpression of histone methyltransferase G9a in HCC, particularly in Myc-driven liver tumors. The increased expression of G9a was associated with poor prognosis and lower survival rates in HCC patients. We also revealed the cooperative interaction between c-Myc and G9a in HCC, highlighting their role in gene repression and cancer development. Additionally, combination therapy targeting G9a and CDK9 showed promising efficacy in patient-derived models of Myc-driven HCC.
MOLECULAR ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jingru Xu, Mengjia Zheng, Dexter Kai Hao Thng, Tan Boon Toh, Lei Zhou, Glenn Kunnath Bonney, Yock Young Dan, Pierce Kah Hoe Chow, Chenjie Xu, Edward Kai-Hua Chow
Summary: SALL4 is an oncofetal protein that drives cancer progression and poor prognosis in hepatocellular carcinoma and hematological malignancies. Due to the lack of well-structured binding pockets, targeted inhibitors for SALL4 are difficult to design. In this study, an AI-assisted platform utilizing molecular beacons and nanodiamonds was developed to evaluate patient-specific drug sensitivity for HCC treatment, providing efficient and rapid clinical decision support.
Review
Oncology
Chin Sern Yiong, Tzu Ping Lin, Vivian Yujing Lim, Tan Boon Toh, Valerie Shiwen Yang
Summary: Sarcomas, a type of cancer of mesenchymal origin, are not well understood. Recent advancements in cancer immunotherapy have shown that immune checkpoint inhibitors may be more effective than traditional chemotherapy in some sarcomas. However, most sarcoma patients do not respond to this treatment, highlighting the need for predictive biomarkers to identify those who will benefit.
BIOMARKER RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Jingru Xu, Mengjie Gu, Lissa Hooi, Tan Boon Toh, Dexter Kai Hao Thng, Jhin Jieh Lim, Edward Kai-Hua Chow
Summary: The study found that nanodiamonds can serve as an efficient drug delivery platform for improving the delivery of siRNA into tumor cells, protecting siRNA from degradation. Compared to other delivery methods, ND delivery of siRNA was more effective at penetrating tumor spheroids and inhibiting tumor cell proliferation.
Article
Gastroenterology & Hepatology
Yong Chun Chong, Tan Boon Toh, Zhiling Chan, Quy Xiao Xuan Lin, Dexter Kai Hao Thng, Lissa Hooi, Zhaobing Ding, Timothy Shuen, Han Chong Toh, Yock Young Dan, Glenn Kunnath Bonney, Lei Zhou, Pierce Chow, Yulan Wang, Touati Benoukraf, Edward Kai-Hua Chow, Weiping Han
HEPATOLOGY COMMUNICATIONS
(2020)
