DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Июль 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.

Язык: Английский

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Molecular targeted therapy for anticancer treatment

Experimental & Molecular Medicine, Год журнала: 2022, Номер 54(10), С. 1670 - 1694

Опубликована: Окт. 12, 2022

Abstract Since the initial clinical approval in late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served a fundamental backbone precision medicine cancer treatment. These approaches are now used clinically first-line various human cancers. Compared to conventional chemotherapy, have efficient with fewer side effects. However, emergence drug resistance is major drawback therapy, several strategies been attempted improve efficacy by overcoming such resistance. Herein, we summarize current knowledge regarding agents, including classification, brief biology target kinases, mechanisms action, examples perspectives future development.

Язык: Английский

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Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer

Nature reviews. Cancer, Год журнала: 2022, Номер 22(6), С. 323 - 339

Опубликована: Март 9, 2022

Язык: Английский

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The expanding universe of PARP1-mediated molecular and therapeutic mechanisms

Molecular Cell, Год журнала: 2022, Номер 82(12), С. 2315 - 2334

Опубликована: Март 9, 2022

Язык: Английский

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Advances in PET imaging of cancer

Nature reviews. Cancer, Год журнала: 2023, Номер 23(7), С. 474 - 490

Опубликована: Май 31, 2023

Язык: Английский

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New and Emerging Targeted Therapies for Advanced Breast Cancer

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(4), С. 2288 - 2288

Опубликована: Фев. 18, 2022

In the United States, breast cancer is among most frequently diagnosed cancers in women. Breast classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including expression of hormone receptors (estrogen and/or progesterone receptor) HER2. Primary treatments can include surgery, radiation therapy, systemic chemotherapy, endocrine targeted therapy. Endocrine therapy has been shown to be effective receptor-positive a common choice for adjuvant However, due aggressive nature triple-negative cancer, becoming noteworthy area research search non-endocrine-targets cancer. addition HER2-targeted other emerging therapies immunotherapy against critical checkpoints pathways cell growth. This review summarizes novel explores possible implications combination

Язык: Английский

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Recent advances in DDR (DNA damage response) inhibitors for cancer therapy

European Journal of Medicinal Chemistry, Год журнала: 2022, Номер 230, С. 114109 - 114109

Опубликована: Янв. 12, 2022

Язык: Английский

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Pan-cancer analysis of post-translational modifications reveals shared patterns of protein regulation

Cell, Год журнала: 2023, Номер 186(18), С. 3945 - 3967.e26

Опубликована: Авг. 1, 2023

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology both normal cancer cells. Advances mass spectrometry enable high-throughput, accurate, sensitive measurement of PTM levels to better understand their role, prevalence, crosstalk. Here, we analyze the largest collection proteogenomics data from 1,110 patients with profiles across 11 types (10 National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns changes protein acetylation phosphorylation involved hallmark processes. These revealed subsets tumors, different types, including those dysregulated DNA repair driven by phosphorylation, altered metabolic regulation associated immune response acetylation, affected kinase specificity crosstalk between modified histone regulation. Overall, this resource highlights rich biology governed PTMs exposes potential new therapeutic avenues.

Язык: Английский

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A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer

Journal of Advanced Research, Год журнала: 2023, Номер 54, С. 271 - 292

Опубликована: Фев. 14, 2023

Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive phenotype of with associated chemoresistance. The development chemo- or radioresistance could be attributed to diverse tumor microenvironments, overexpression membrane proteins (transporters), epigenetic changes, and alteration the cell signaling pathways/genes stem cells (CSCs). Due heterogeneous nature TNBC, therapeutic response existing modalities offers limited scope thus results in reccurance after therapy. To establish landmark efficacy, number novel have been proposed. In addition, reversal resistance that developed during treatment may altered by employing appropriate modalities. This review aims discuss plethora investigations carried out, which will help readers understand make an choice therapy directed toward complete elimination TNBC. manuscript addresses major contributory factors from microenvironment are responsible for chemoresistance poor prognosis. cellular events molecular mechanism-based interventions explained detail. Inhibition ABC transporters, pathways CSCs, modification promising this regard. TNBC progression, invasion, metastasis recurrence can also inhibited blocking multiple pathways, targeting specific receptors/epigenetic targets, disrupting bioenergetics generating reactive oxygen species (ROS).

Язык: Английский

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PROTAC’ing oncoproteins: targeted protein degradation for cancer therapy

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Март 30, 2023

Molecularly targeted cancer therapies substantially improve patient outcomes, although the durability of their effectiveness can be limited. Resistance to these is often related adaptive changes in target oncoprotein which reduce binding affinity. The arsenal therapies, moreover, lacks coverage several notorious oncoproteins with challenging features for inhibitor development. Degraders are a relatively new therapeutic modality deplete protein by hijacking cellular destruction machinery. offer advantages therapy including resiliency acquired mutations protein, enhanced selectivity, lower dosing requirements, and potential abrogate oncogenic transcription factors scaffolding proteins. Herein, we review development proteolysis targeting chimeras (PROTACs) selected targets reported biological activities. medicinal chemistry PROTAC design has been area active research, but recent advances field will usher an era rational degrader design.

Язык: Английский

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