Transcription Factors and Cancer

The Cancer Journal, Journal Year: 2023, Volume and Issue: 29(1), P. 38 - 46

Published: Jan. 1, 2023

Abstract Cancer is defined by the presence of uncontrollable cell growth, whereby improper proliferative signaling has overcome regulation cellular mechanisms. Transcription factors are uniquely situated at helm signaling, merging extracellular stimuli with intracellular responses. Therefore, this class proteins plays a pivotal role in coordinating correct gene expression levels for maintaining normal functions. Dysregulation transcription factor activity unsurprisingly drives tumorigenesis and oncogenic transformation. Although imparts considerable therapeutic potential to targeting factors, their lack enzymatic renders intervention challenging contributed sense that “undruggable.” Yet, enduring efforts elucidate strategies as well deeper understanding interactions binding partners have led advancements emerging counter narrative. Here, we highlight some these approaches, focusing primarily on therapeutics advanced clinic.

Language: Английский

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Role of bromodomain and extraterminal (BET) proteins in prostate cancer

Expert Opinion on Investigational Drugs, Journal Year: 2023, Volume and Issue: 32(3), P. 213 - 228

Published: March 1, 2023

Introduction The bromodomain and extraterminal (BET) family of proteins are epigenetic readers acetylated histones critical activators oncogenic networks across many cancers. Therapeutic targeting BET has been an attractive area clinical development for metastatic castration-resistant prostate cancer. In recent years, structurally diverse inhibitors have discovered tested. Preclinical studies demonstrated significant antiproliferative activity against However, their success as monotherapies limited by treatment-associated toxicities, primary acquired drug resistance, a lack predictive biomarkers benefit.Areas covered This review provides overview advancements in inhibitor design, preclinical research, conclusions from trials We speculate on incorporating into combination regimens with other agents to improve the therapeutic index inhibition treating cancer.Expert opinion potential cancer studies. further research is needed identify that can predict sensitivity develop novel, highly selective reduce toxicities. Finally, likely hold most agents.

Language: Английский

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Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

Cancers, Journal Year: 2022, Volume and Issue: 14(24), P. 6026 - 6026

Published: Dec. 7, 2022

Resistance to death is one of the hallmarks human B cell malignancies and often contributes lack a lasting response today's commonly used treatments. Drug discovery approaches designed activate machinery have generated large number inhibitors anti-apoptotic proteins from B-cell lymphoma/leukemia 2 family receptor (BCR) signaling pathway. Orally administered small-molecule Bcl-2 protein BCR partners (e.g., Bruton's tyrosine kinase phosphatidylinositol-3 kinase) already been included (as monotherapies or combination therapies) in standard care for selected malignancies. Agonistic monoclonal antibodies their derivatives (antibody-drug conjugates, antibody-radioisotope bispecific T engagers, chimeric antigen receptor-modified cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, CD38) are indicated treatment patients with tumors. However, given that some either refractory current therapies relapse after treatment, novel therapeutic strategies needed. Here, we review managing malignancies, focus on ongoing clinical development more effective, selective drugs these molecules, well other TAAs proteins. The observed impact metabolic reprogramming pathophysiology highlights promise checkpoints disorders.

Language: Английский

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Targeting Epigenetic Mechanisms: A Boon for Cancer Immunotherapy

Biomedicines, Journal Year: 2023, Volume and Issue: 11(1), P. 169 - 169

Published: Jan. 9, 2023

Immunotherapy is rapidly emerging as a promising approach against cancer. In the last decade, various immunological mechanisms have been targeted to induce an increase in immune response cancer cells. However, despite results, many patients show partial response, resistance, or serious toxicities. A way overcome this use of immunotherapeutic approaches, combination with other potential therapeutic approaches. Aberrant epigenetic modifications play important role carcinogenesis and its progression, well functioning Thus, approaches targeting aberrant might provide effective antitumor effect. Further, recent development potent drugs immunomodulators gives hope combinatorial approach. review, we summarize synergy mechanism between therapies immunotherapy for treatment cancer, discuss advancements translation

Language: Английский

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From PROTAC to inhibitor: Structure-guided discovery of potent and orally bioavailable BET inhibitors

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 251, P. 115246 - 115246

Published: March 4, 2023

Language: Английский

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