Cell cycle control in cancer

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 74 - 88

Published: Sept. 10, 2021

Language: Английский

---

Targeting mutant p53 for cancer therapy: direct and indirect strategies

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Sept. 28, 2021

TP53 is a critical tumor-suppressor gene that mutated in more than half of all human cancers. Mutations not only impair its antitumor activity, but also confer mutant p53 protein oncogenic properties. The p53-targeted therapy approach began with the identification compounds capable restoring/reactivating wild-type functions or eliminating p53. Treatments directly target are extremely structure and drug-species-dependent. Due to mutation p53, multiple survival pathways normally maintained by disrupted, necessitating activation compensatory genes promote cancer cell survival. Additionally, because contribute proliferation metastasis, targeting signaling altered appears be an attractive strategy. Synthetic lethality implies while disruption either alone permissible among two synthetic lethal interactions, complete both results death. Thus, rather exploiting may provide additional therapeutic benefits. research progress on noncoding RNAs has made it clear disrupting RNA networks favorable effect, supporting hypothesis have potential effects cancers mutations. purpose this review discuss treatments for focus restoring functions, interactions possibility acting as targets will discussed.

Language: Английский

---

Gain-of-function mutant p53 in cancer progression and therapy

Journal of Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 12(9), P. 674 - 687

Published: July 21, 2020

Abstract p53 is a key tumor suppressor, and loss of function frequently prerequisite for cancer development. The gene the most mutated in human cancers; mutations occur >50% all cancers almost every type cancers. Most are missense mutations, which produce full-length mutant (mutp53) protein with only one amino acid difference from wild-type protein. In addition to tumor-suppressive p53, many mutp53 proteins acquire new oncogenic activities independently promote progression, termed gain-of-function (GOF). Mutp53 often accumulates very high levels cells, critical its GOF. Given mutation frequency GOF cancer, therapies targeting have attracted great interest. Further understanding mechanisms underlying accumulation will help develop effective treating containing mutp53. this review, we summarize recent advances studies on regulation as well

Language: Английский

---

A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Sept. 21, 2020

Abstract The inhibition of the DNA damage response (DDR) pathway in treatment cancer has recently gained interest, and different DDR inhibitors have been developed. Among them, most promising ones target WEE1 kinase family, which a crucial role cell cycle regulation identification repair both nonmalignant cells. This review recapitulates discusses recent findings on biological function WEE1/PKMYT1 during repair, with focus their dual as tumor suppressors cells pseudo-oncogenes We here report available data molecular functional alterations kinases hematological solid tumors. Moreover, we summarize preclinical information 36 chemo/radiotherapy agents, particular effect checkpoints cellular WEE1/PKMYT1-dependent response. Finally, this outlines important pre-clinical clinical efficacy monotherapy combination agents or other selective currently used under evaluation for patients.

Language: Английский

---

Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells

Pharmacological Research, Journal Year: 2022, Volume and Issue: 181, P. 106270 - 106270

Published: May 21, 2022

Language: Английский

---

Selective Autophagy Regulates Cell Cycle in Cancer Therapy

Theranostics, Journal Year: 2018, Volume and Issue: 9(1), P. 104 - 125

Published: Dec. 19, 2018

Aberrant function of cell cycle regulators results in uncontrolled proliferation, making them attractive therapeutic targets cancer treatment.Indeed, survival many cancers exclusively relies on these proteins, and several specific inhibitors are clinical use.Although the ubiquitin-proteasome system is responsible for periodic quality control proteins during progression, increasing evidence clearly demonstrates intimate interaction between regulation selective autophagy, important homeostasis maintenance machinery.However, studies have often led to divergent rather than unifying explanations due complexity autophagy signaling network, inconsistent functions general different characteristics autophagic substrates.In this review, we highlight current data illustrating contradictory role regulating autophagy.We also focus how acts as a central mechanism maintain orderly DNA repair genome integrity by degrading division, promoting damage repair.We further discuss ways which may impact regulators, since failure appropriately remove can interfere with death-related processes, including senescence autophagy-related death.Imbalanced proliferation typically utilized cells acquire resistance.Finally, possibility potent anticancer strategy that or together.

Language: Английский

---

Tumor biomarkers for diagnosis, prognosis and targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

---

New Horizons in Lung Cancer Management Through ATR/CHK1 Pathway Modulation

Future Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 15(19), P. 1807 - 1818

Published: Oct. 1, 2023

Lung cancer is the leading cause of cancer-related deaths worldwide. Molecular profiling has contributed to a new classification lung cancer, driving advancements in research and therapy. The ataxia telangiectasia rad3/checkpoint kinase 1 (ATR/CHK1) pathway plays crucial role maintaining genomic stability, its activation been linked development drug resistance poor prognosis. Clinical preclinical studies have demonstrated promising results targeting this pathway. ATR CHK1 are proteins that collaborate repair DNA damage caused by radiation or chemotherapy. ATR/CHK1 inhibitors currently under investigation clinical trials. This article explores potential for treating cancer.

Language: Английский

---

DNA Damage and Its Role in Cancer Therapeutics

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

---

Defining and Modulating ‘BRCAness’

Trends in Cell Biology, Journal Year: 2019, Volume and Issue: 29(9), P. 740 - 751

Published: July 27, 2019

Language: Английский

---