Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism DOI Open Access

Seo-Young Koo,

Eun‐Ji Park,

Hyun-Ji Noh

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8441 - 8441

Published: May 8, 2023

Changes in the DNA damage response (DDR) and cellular metabolism are two important factors that allow cancer cells to proliferate. DDR is a set of events which recognized, repair recruited site damage, lesion repaired, responses associated with processed. In cancer, commonly dysregulated, enzymes prone changes ubiquitination. Additionally, metabolism, especially glycolysis, upregulated cells, this metabolic pathway modulated by The ubiquitin-proteasome system (UPS), particularly E3 ligases, act as bridge between since they regulate processes. Hence, ligases high substrate specificity considered potential therapeutic targets for treating cancer. A number small molecule inhibitors designed target different components UPS have been developed, several tested clinical trials human use. review, we discuss role ubiquitination on overall confirm link them through NEDD4, APC/CCDH1, FBXW7, Pellino1. addition, present an overview clinically implications their practical

Language: Английский

DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy DOI Creative Commons
Ruixue Huang, Ping‐Kun Zhou

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 9, 2021

Abstract Genomic instability is the hallmark of various cancers with increasing accumulation DNA damage. The application radiotherapy and chemotherapy in cancer treatment typically based on this property cancers. However, adverse effects including normal tissues injury are also accompanied by chemotherapy. Targeted therapy has potential to suppress cells’ damage response through tailoring patients lacking specific functions. Obviously, understanding broader role repair became a basic attractive strategy for targeted therapy, particular, raising novel hypothesis or theory field basis previous scientists’ findings would be important future promising druggable emerging targets. In review, we first illustrate timeline steps roles promotion developed, then summarize mechanisms regarding associated highlighting proteins behind targeting that initiate functioning abnormally duo extrinsic harm environmental factors, also, baseline drift leads harmful intrinsic therapy. addition, clinical therapeutic drugs effects, as well scheme relative trials were intensive discussed. Based background, suggest two hypotheses, namely “environmental gear selection” describe pathway evolution, “DNA drift”, which may play magnified mediating during treatment. This new shed light provide much better more comprehensive holistic view promote development research direction overcoming strategies patients.

Language: Английский

Citations

515
Gallbladder cancer DOI
Juan Carlos Roa, Patricia García, Vinay K. Kapoor

et al.

Nature Reviews Disease Primers, Journal Year: 2022, Volume and Issue: 8(1)

Published: Oct. 27, 2022

Language: Английский

Citations

193
DNA Damage and Its Role in Cancer Therapeutics DOI Open Access
Jaeyoung Moon,

Ichiwa Kitty,

Kusuma Renata

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4741 - 4741

Published: March 1, 2023

DNA damage is a double-edged sword in cancer cells. On the one hand, exacerbates gene mutation frequency and risk. Mutations key repair genes, such as breast 1 (BRCA1) and/or 2 (BRCA2), induce genomic instability promote tumorigenesis. other induction of using chemical reagents or radiation kills cells effectively. Cancer-burdening mutations repair-related genes imply relatively high sensitivity to chemotherapy radiotherapy because reduced efficiency. Therefore, designing specific inhibitors targeting enzymes pathway an effective way synthetic lethality with therapeutics. This study reviews general pathways involved potential proteins that could be targeted for

Language: Английский

Citations

42
Assessment of the electrostatic binding of ferrocenylmethyl-nitroaniline derivatives to DNA: A combined experimental and theoretical study DOI
Touhami Lanez, Mehran Feizi‐Dehnayebi, Elhafnaoui Lanez

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1308, P. 138386 - 138386

Published: April 25, 2024

Language: Английский

Citations

34
Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells DOI Open Access
Pankaj Garg, Jyoti Malhotra, Prakash Kulkarni

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2478 - 2478

Published: July 7, 2024

The rise of drug resistance in cancer cells presents a formidable challenge modern oncology, necessitating the exploration innovative therapeutic strategies. This review investigates latest advancements overcoming mechanisms employed by cells, focusing on emerging modalities. intricate molecular insights into resistance, including genetic mutations, efflux pumps, altered signaling pathways, and microenvironmental influences, are discussed. Furthermore, promising avenues offered targeted therapies, combination treatments, immunotherapies, precision medicine approaches highlighted. Specifically, synergistic effects combining traditional cytotoxic agents with molecularly inhibitors to circumvent pathways examined. Additionally, evolving landscape immunotherapeutic interventions, immune checkpoint adoptive cell is explored terms bolstering anti-tumor responses evasion mechanisms. Moreover, significance biomarker-driven strategies for predicting monitoring treatment underscored, thereby optimizing outcomes. For future direction paradigms, current focused prevailing challenges improving patient outcomes, through an integrative analysis these

Language: Английский

Citations

34
Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy DOI Open Access
Giorgio Valabrega,

Giulia Scotto,

Valentina Tuninetti

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(8), P. 4203 - 4203

Published: April 19, 2021

Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) able to interact with the binding site cofactor (NAD+) trapping on DNA. In this way, they inhibit single-strand repair. These drugs have been approved in recent years treatment of ovarian cancer. Although share some similarities, from point view chemical structure pharmacodynamic, pharmacokinetic properties, these also substantial differences. differences may underlie different safety profiles activity PARPi.

Language: Английский

Citations

77
Unboxing the molecular modalities of mutagens in cancer DOI Open Access
Smita Kumari, Sudhanshu Sharma, Dia Advani

et al.

Environmental Science and Pollution Research, Journal Year: 2021, Volume and Issue: 29(41), P. 62111 - 62159

Published: Oct. 5, 2021

Language: Английский

Citations

73
The cell cycle, cancer development and therapy DOI

Elaheh Jamasbi,

Mona Hamelian, Mohammed Akhter Hossain

et al.

Molecular Biology Reports, Journal Year: 2022, Volume and Issue: 49(11), P. 10875 - 10883

Published: Aug. 5, 2022

Language: Английский

Citations

67
Cellular senescence in the aging brain: A promising target for neurodegenerative diseases DOI
Manas Ranjan Sahu,

Linchi Rani,

Rhea Subba

et al.

Mechanisms of Ageing and Development, Journal Year: 2022, Volume and Issue: 204, P. 111675 - 111675

Published: April 14, 2022

Language: Английский

Citations

47
The Promise of Nanoparticles-Based Radiotherapy in Cancer Treatment DOI Open Access
Munima Haque, Md Salman Shakil, Kazi Mustafa Mahmud

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(6), P. 1892 - 1892

Published: March 22, 2023

Radiation has been utilized for a long time the treatment of cancer patients. However, radiotherapy (RT) many constraints, among which non-selectivity is primary one. The implementation nanoparticles (NPs) with RT not only localizes radiation in targeted tissue but also provides significant tumoricidal effect(s) compared to alone. NPs can be functionalized both biomolecules and therapeutic agents, their combination significantly reduces side effects RT. NP-based destroys cells through multiple mechanisms, including ROS generation, turn damages DNA other cellular organelles, inhibiting double-strand damage-repair system, obstructing cell cycle, regulating tumor microenvironment, killing stem cells. Furthermore, such combined treatments overcome radioresistance drug resistance chemotherapy. Additionally, have shown synergistic benefit(s) enhanced window. phototherapy, i.e., photodynamic therapy photothermal RT, phototoxicity offers excellent benefits. Moreover, using promise outcomes clinical trials. Therefore, extensive research this field will pave way toward improved treatment.

Language: Английский

Citations

36