Review
Genetics & Heredity
Malgorzata Drzewiecka, Gabriela Barszczewska-Pietraszek, Piotr Czarny, Tomasz Skorski, Tomasz Sliwinski
Summary: Research studies on synthetic lethality in human cells aim to develop effective and safe anti-cancer chemotherapy. DNA repair factors, especially those involved in double-strand break repair, are the primary targets for inducing the synthetic lethality effect. Inhibition of RAD52 and/or PARP1 has shown promise as a potential target for inducing synthetic lethality in tumor cells with deficiencies in the canonical repair pathways. However, resistance to PARP1 inhibitors poses a major obstacle to successful treatment protocols. DNA polymerase theta (Pol theta) plays a key role in an alternative DSB repair pathway and its inhibition holds potential for inducing synthetic lethality in tumors with homologous recombination repair deficiencies.
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)
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.
Article
Biochemistry & Molecular Biology
Raquel Gago-Fuentes, Valentyn Oksenych
Summary: NHEJ factors XLF, DNA-PKcs, and PAXX play crucial roles in maintaining neural stem and progenitor cell populations and neurodevelopment in mammals, particularly evident in double knockout models.
Article
Chemistry, Medicinal
Cheng Wang, Lailiang Qu, Shang Li, Fucheng Yin, Limei Ji, Wan Peng, Heng Luo, Dehua Lu, Xingchen Liu, Xinye Chen, Lingyi Kong, Xiaobing Wang
Summary: The dual action of PARP inhibitors and EZH2 inhibitors can enhance the treatment of TNBC, with the compound 5a showing potential in reducing sensitivity to inhibitors in BRCA cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Bac Viet Le, Paulina Podszywalow-Bartnicka, Katarzyna Piwocka, Tomasz Skorski
Summary: PARP inhibitors are crucial in treating BRCA1/2-mutated/deficient malignancies, but the emergence of resistance poses a challenge, requiring further research on therapeutic strategies to overcome this issue.
Review
Oncology
Amrita Roy, Soumen Bera, Luciano Saso, Bilikere S. Dwarakanath
Summary: Autophagy is a cellular process that recycles damaged materials to generate precursors for biosynthesis, playing an important role in cellular responses to stress. While successful autophagy promotes cell survival, interruptions in autophagy can lead to cell death. Clinical trials using autophagy modifiers to enhance radiotherapy efficacy have yielded equivocal results, raising concerns about their use as adjuvants. Understanding the biology of cancer cells and their microenvironment is crucial for the success of autophagy modifiers as anticancer agents.
FRONTIERS IN ONCOLOGY
(2022)
Article
Microbiology
Walason Abjaude, Bruna Prati, Veridiana Munford, Aline Montenegro, Vanesca Lino, Suellen Herbster, Tatiana Rabachini, Lara Termini, Carlos Frederico Martins Menck, Enrique Boccardo
Summary: Infection with certain types of HPV can lead to various cancers, including cervical cancer. The DNA repair machinery plays a crucial role in both HPV replication and tumor cell survival. In this study, we identified that inhibition of the ATM/CHK2/BRCA1 pathway selectively affects the proliferation of cervical cancer cells, suggesting a potential therapeutic target for cervical cancer and other HPV-associated tumors.
Article
Toxicology
Ezgi Eyluel Bankoglu, Carolin Schuele, Helga Stopper
Summary: The comet assay is widely used in basic research, genotoxicity testing, and human biomonitoring. The study found that DNA damage exceeding 20-30% tail DNA caused more than 50% of cells to die, with etoposide causing slightly more cell death than H2O2 or MMS. Cells showed some repair capacity for DNA damage within a few hours after substance removal.
ARCHIVES OF TOXICOLOGY
(2021)
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.
Review
Biochemistry & Molecular Biology
Rhys Gillman, Kylie Lopes Floro, Miriam Wankell, Lionel Hebbard
Summary: Hepatocellular carcinoma is rapidly becoming a major cause of global mortality due to the increasing prevalence of obesity. DNA damage and repair pathways play important roles in the initiation of liver cancer, yet many contemporary reports neglect the individual pathways in their hypotheses.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Article
Food Science & Technology
S. Ahmad, M. L. Tan, Shahrul Hamid
Summary: Cardiovascular disease is a leading global cause of death, influenced by factors such as genetics, high-fat intake, smoking, hypertension, diabetes, and lifestyle. The disease is caused by the sudden production of reactive oxygen species, resulting in DNA damage and cell death. Various forms of DNA damage have been associated with cardiovascular disease. Therefore, reducing reactive oxygen species is crucial, and nutraceuticals and their bioactive compounds play a role in mitigating DNA damage.
JOURNAL OF FUNCTIONAL FOODS
(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
Plant Sciences
Xin-Yu Li, Xuan Cui, Chang-Quan Xie, Yong Wu, Tang Song, Jin-Di He, Ji Feng, Qian-Ru Cui, Jin-Lian Bin, Qiu-Yun Li, Cheng Xiao, Jing-Huan Deng, Guo-Dong Lu, Jing Zhou
Summary: This study investigates the molecular mechanisms by which Andro and its effects on HCC cell death. It is found that Andro induces HCC cell death through DNA damage and cell cycle arrest, with p53 and p62 playing important roles in this process. Additionally, Andro-induced p62 aggregation leads to the degradation of proteins involved in DNA damage repair. These findings provide valuable insights for repurposing Andro for HCC treatment, regardless of the presence of functional p53.
Article
Engineering, Biomedical
Qi Xu, Hao Zhang, Hanghang Liu, Yaobao Han, Weibao Qiu, Zhen Li
Summary: The study reveals a novel mechanism of core-shell copper selenide coated gold nanoparticles inhibiting the protective autophagy and DNA repair of tumor cells, significantly enhancing the radiotherapy efficacy of glioblastoma.
Article
Biochemistry & Molecular Biology
Natalia Riera-Heredia, Esmail Lutfi, Sara Balbuena-Pecino, Emilio J. Velez, Karine Dias, Florian Beaumatin, Joaquim Gutierrez, Iban Seiliez, Encarnacion Capilla, Isabel Navarro
Summary: The study revealed the involvement of key adipogenic and autophagy-related genes in rainbow trout adipocyte differentiation, indicating a possible role of autophagy during adipogenesis. Additionally, the delay in adipogenesis process by incubating preadipocytes with lysosomal inhibitors suggests a relationship between autophagy and adipocyte differentiation.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Valentin J. A. Barthet, Michaela Mrschtik, Elzbieta Kania, David G. McEwan, Dan Croft, James O'Prey, Jaclyn S. Long, Kevin M. Ryan
Summary: DRAM-4 and DRAM-5 are nutrient-responsive members of the DRAM family that exhibit interconnected roles in the regulation of autophagy and cell survival under nutrient-deprived conditions.
Review
Biochemistry & Molecular Biology
David G. McEwan, Kevin Ryan
Summary: Communication between organelles is crucial for cellular homeostasis, with recent findings showing that molecular bridges containing N-terminal Chorein/VPS13 domains play a key role in directing lipid traffic between organelles. These bridges are evolutionarily conserved and present in proteins involved in endocytic and autophagy pathways. Research has highlighted the essential role of Chorein-N domain containing ATG2 proteins in autophagosome formation and the transport of lipids from the endoplasmic reticulum. The study also explores the function of VPS13 proteins in organelle contacts and endocytic pathways, as well as the disruption of these processes by disease-causing mutations.
Review
Biochemistry & Molecular Biology
David A. Gillespie
Summary: Two recent reports demonstrate that heritable, gain-of-function mutations within the Chk1 C-terminal regulatory domain can cause female infertility. Treatment with selective Chk1 inhibitor drugs can rescue this mutation and allow embryos to develop normally.
Editorial Material
Oncology
Kevin M. Ryan
MOLECULAR ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Jaclyn S. Long, Elzbieta Kania, David G. McEwan, Valentin J. A. Barthet, Martina Brucoli, Marcus J. G. W. Ladds, Christoph Nossing, Kevin M. Ryan
Summary: Research findings show that the loss of Atg7 in a model of PDAC with mutant Kras(G12D) and mutant Trp53(172H/+) promotes tumor development and enhances metastasis, while reducing the occurrence of metastasis. Tumors with Atg7(+/-) have lower levels of succinate and lower invasion capabilities.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Alice D. Baudot, Victoria M-Y Wang, Josh D. Leach, Jim O'Prey, Jaclyn S. Long, Viola Paulus-Hock, Sergio Lilla, David M. Thomson, John Greenhorn, Farah Ghaffar, Colin Nixon, Miep H. Helfrich, Douglas Strathdee, Judith Pratt, Francesco Marchesi, Sara Zanivan, Kevin M. Ryan
Summary: This study reveals the importance of glycan degradation in macroautophagy. The absence of the glycosidase FUCA1 leads to lysosomal glycan accumulation and impaired autophagic flux. Dysregulated glycan degradation hinders autophagosome-lysosome fusion and contributes to the pathology of fucosidosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Christoph Nossing, Kevin M. Ryan
Summary: Cell death, known as apoptosis, is a crucial process in the lifecycle of multicellular organisms. Kerr, Wyllie and Currie were the first to define and describe the distinct morphological features of controlled cell death, and they also recognized its potential in cancer therapy and its occurrence during cancer development. This article reevaluates their initial assumptions and concepts about apoptosis in the context of modern biology, 50 years after its original publication.
BRITISH JOURNAL OF CANCER
(2023)
Editorial Material
Oncology
Kevin M. Ryan
Summary: A central aspect of scientific research is the sharing of discoveries. Scientists traditionally disseminated their findings through conferences and journal publications. Today, sharing ideas and early data through events and digital platforms such as social media has become more common. The ability to generate and analyze large datasets has revolutionized scientific questions, but managing and sharing the data, as well as legal considerations such as GDPR, remain challenges.
MOLECULAR ONCOLOGY
(2023)
Editorial Material
Oncology
Kevin M. Ryan, Jane Smith, Rene Bernards
Summary: The formation of organizations and societies in scientific research facilitates communication, collaboration, and career development. Partnerships between organizations can further enhance these benefits. This article highlights a new partnership between the European Association for Cancer Research (EACR) and Molecular Oncology, a journal owned by the Federation of European Biochemical Societies (FEBS).
MOLECULAR ONCOLOGY
(2023)
Review
Cell Biology
Jayanta Debnath, Noor Gammoh, Kevin M. Ryan
Summary: Autophagy plays both tumour-suppressive and tumour-promoting roles in cancer, depending on disease stage and mutational background. It is crucial for maintaining cellular homeostasis and cell viability by degrading and recycling cellular cargoes. Recent studies have also revealed its functions in the tumour microenvironment and immune cells, as well as the existence of autophagy-related pathways that contribute to malignant disease. Understanding the impact of autophagy on cancer development and progression has informed the development of anticancer therapies targeting autophagy processes.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Cell Biology
Emilio J. Velez, Simon Schnebert, Maxime Goguet, Sara Balbuena-Pecino, Karine Dias, Linda Beauclair, Stephanie Fontagne-Dicharry, Vincent Veron, Alexandra Depince, Florian Beaumatin, Amaury Herpin, Iban Seiliez
Summary: This study reveals the existence of chaperone-mediated autophagy (CMA) activity in rainbow trout (RT) and highlights its important protective role against stress induced by high glucose levels. The activation of CMA in response to high glucose was found to be mediated by mitochondrial reactive oxygen species and involving the antioxidant transcription factor Nfe2l2/Nrf2. This research provides insights into the role and regulation of CMA in glucose-related metabolic disorders.
Article
Cell Biology
Jake Cross, Joanne Durgan, David G. McEwan, Matthew Tayler, Kevin M. Ryan, Oliver Florey
Summary: Cross et al. demonstrate that non-canonical autophagy activation is responsible for the majority of ATG8 lipidation in response to lysosome damage, rather than lysophagy. They show that ATG8 proteins directly conjugate to lysosomal membranes and interact with the lipid transfer protein ATG2. This study reveals a parallel ATG8 response to lysosome damage that is mechanistically distinct from lysophagy and involves important links to lipid transfer and dynamics.
JOURNAL OF CELL BIOLOGY
(2023)