Chronotype and Cancer: Emerging Relation Between Chrononutrition and Oncology from Human Studies DOI Open Access
Justyna Godos, Walter Currenti, Raffaele Ferri

и другие.

Nutrients, Год журнала: 2025, Номер 17(3), С. 529 - 529

Опубликована: Янв. 31, 2025

Fasting-feeding timing is a crucial pattern implicated in the regulation of daily circadian rhythms. The interplay between sleep and meal underscores importance maintaining alignment order to avoid creating metabolic environment conducive carcinogenesis following molecular systemic disruption performance immune function. chronicity such condition may support initiation progression cancer through variety mechanisms, including increased oxidative stress, suppression, activation proliferative signaling pathways. This review aims summarize current evidence from human studies provide an overview potential mechanisms underscoring role chrononutrition (including time-restricted eating) on risk. Current shows that morning chronotype, suggesting physiological rhythms eating timing, associated with lower risk cancer. Also, early prolonged nighttime fasting were also suggests chronotype influences cell cycle regulation, modulation pathways inflammation, gut microbiota fluctuations. In conclusion, although there are no clear guidelines this matter, emerging supports hypothesis time-related (i.e., time/calorie-restricted feeding intermittent/periodic fasting) could potentially lead reduced

Язык: Английский

Therapeutic targeting of “undruggable” MYC DOI
Víctor Llombart, Marc R. Mansour

EBioMedicine, Год журнала: 2021, Номер 75, С. 103756 - 103756

Опубликована: Дек. 20, 2021

Язык: Английский

Процитировано

276
PROTACs: great opportunities for academia and industry (an update from 2020 to 2021) DOI Creative Commons

Ming He,

Chao-Guo Cao, Zhihao Ni

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июнь 9, 2022

Abstract PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through ubiquitin–proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such cancer, immune disorders, viral infections, neurodegenerative diseases, but also provide unique chemical knockdown tools biological research catalytic, reversible, rapid manner. In 2019, our group published review article “PROTACs: great opportunities academia industry” journal, summarizing representative compounds reported before end 2019. past 2 years, entire field protein experienced development, including large increase number papers on small-molecule degraders have entered will enter stage. addition PROTAC molecular glue technology, other technologies are developing rapidly. this article, we mainly summarize related targets 2020–2021 present researchers exciting developments degradation. The problems need solved briefly introduced.

Язык: Английский

Процитировано

179
Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment DOI
Giulia Petroni,

Aitziber Buqué,

Lisa M. Coussens

и другие.

Nature Reviews Drug Discovery, Год журнала: 2022, Номер 21(6), С. 440 - 462

Опубликована: Март 15, 2022

Язык: Английский

Процитировано

103
Reprogramming tumour-associated macrophages to outcompete cancer cells DOI
Xian Zhang, Shun Li,

Isha Malik

и другие.

Nature, Год журнала: 2023, Номер 619(7970), С. 616 - 623

Опубликована: Июнь 28, 2023

Язык: Английский

Процитировано

88
Harnessing TRAIL-induced cell death for cancer therapy: a long walk with thrilling discoveries DOI Creative Commons
Antonella Montinaro, Henning Walczak

Cell Death and Differentiation, Год журнала: 2022, Номер 30(2), С. 237 - 249

Опубликована: Окт. 4, 2022

Abstract Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) can induce in a wide variety of cancer cells, both vitro and vivo, importantly without killing any essential normal cells. These findings formed the basis for development TRAIL-receptor agonists (TRAs) therapy. However, clinical trials conducted with different types TRAs have, thus far, afforded only limited therapeutic benefit, as either respectively chosen agonist showed insufficient anticancer activity or signs toxicity, right TRAIL-comprising combination therapy was not employed. Therefore, this review we will discuss molecular determinants TRAIL resistance, most promising TRAIL-sensitizing agents discovered to date and, importantly, whether these could also prove therapeutically efficacious upon relapse following conventional first-line therapies. We more recent progress made regards highly active non-immunogenic next generation TRAs. Based thereupon, propose how resistance might be successfully overcome, leading possible future potent, cancer-selective therapies that are based on our current understanding biology TRAIL-induced cell death. It is such may offer opportunity tackle one major obstacles effective therapy, namely overcoming chemo- and/or targeted-therapy resistance. Even if were achievable certain particular cancer, would significant meaningful achievement.

Язык: Английский

Процитировано

83
Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies DOI Creative Commons
Qian Liu, Jing Zhang, Chenchen Guo

и другие.

Cell, Год журнала: 2024, Номер 187(1), С. 184 - 203.e28

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

74
Immunologic tumor microenvironment modulators for turning cold tumors hot DOI Creative Commons
Gholamreza Khosravi, Samaneh Mostafavi,

Sanaz Bastan

и другие.

Cancer Communications, Год журнала: 2024, Номер 44(5), С. 521 - 553

Опубликована: Март 29, 2024

Abstract Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within tumor microenvironment (TME). Hot tumors, characterized by heightened activity responsiveness to checkpoint inhibitors (ICIs), stand in stark contrast cold which lack infiltration remain resistant therapy. To overcome evasion mechanisms employed cells, novel immunologic modulators have emerged, particularly ICIs targeting T‐lymphocyte‐associated protein 4 (CTLA‐4) programmed cell death 1/programmed death‐ligand 1(PD‐1/PD‐L1). These agents disrupt inhibitory signals reactivate system, transforming tumors hot ones promoting effective antitumor responses. However, challenges persist, including primary resistance immunotherapy, autoimmune side effects, response heterogeneity. Addressing these requires innovative strategies, deeper mechanistic insights, a combination interventions enhance effectiveness immunotherapies. In landscape cancer medicine, where represent formidable hurdle, understanding TME harnessing its potential reprogram is paramount. This review sheds light current advancements future directions quest for more safer treatment offering hope patients with immune‐resistant tumors.

Язык: Английский

Процитировано

74
c-Myc-Targeting PROTAC Based on a TNA-DNA Bivalent Binder for Combination Therapy of Triple-Negative Breast Cancer DOI
Xintong Li, Ze Zhang,

Fangyan Gao

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(16), С. 9334 - 9342

Опубликована: Апрель 17, 2023

Triple-negative breast cancer (TNBC) is highly aggressive with a poor clinical prognosis and no targeted therapy. The c-Myc protein master transcription factor potential therapeutic target for TNBC. In this study, we develop PROTAC (PROteolysis TArgeting Chimera) based on TNA (threose nucleic acid) DNA that effectively targets degrades c-Myc. aptamer selected in vitro to bind the c-Myc/Max heterodimer appended E-box sequence create high-affinity, biologically stable bivalent binder. TNA-E box-pomalidomide (TEP) conjugate specifically endogenous c-Myc/Max, inhibits TNBC cell proliferation, sensitizes cells cyclin-dependent kinase inhibitor palbociclib vitro. mouse model, combination therapy TEP potently suppresses tumor growth. This study offers promising acid-based modality both chemical biology studies interventions of

Язык: Английский

Процитировано

72
MYC targeting by OMO-103 in solid tumors: a phase 1 trial DOI Creative Commons
Elena Garralda, Marie‐Eve Beaulieu, Víctor Moreno

и другие.

Nature Medicine, Год журнала: 2024, Номер 30(3), С. 762 - 771

Опубликована: Фев. 6, 2024

Abstract Among the ‘most wanted’ targets in cancer therapy is oncogene MYC, which coordinates key transcriptional programs tumor development and maintenance. It has, however, long been considered undruggable. OMO-103 a MYC inhibitor consisting of 91-amino acid miniprotein. Here we present results from phase 1 study advanced solid tumors, established to examine safety tolerability as primary outcomes pharmacokinetics, recommended 2 dose preliminary signs activity secondary ones. A classical 3 + design was used for escalation weekly intravenous, single-agent administration 21-day cycles, encompassing six levels (DLs). total 22 patients were enrolled, with treatment maintained until disease progression. The most common adverse events grade infusion-related reactions, occurring ten patients. One dose-limiting toxicity occurred at DL5. Pharmacokinetics showed nonlinearity, tissue saturation DL5 terminal half-life serum 40 h. Of 19 evaluable response, 12 reached predefined 9-week time point assessment drug antitumor activity, eight those showing stable by computed tomography. patient defined response evaluation criteria tumors 49% reduction volume best response. Transcriptomic analysis supported target engagement biopsies. In addition, identified soluble factors that are potential pharmacodynamic predictive markers. Based on all these data, determined (6.48 mg kg −1 ). ClinicalTrials.gov identifier: NCT04808362 .

Язык: Английский

Процитировано

71
Cooperation between bHLH transcription factors and histones for DNA access DOI Creative Commons
Alicia K. Michael,

Lisa Stoos,

Priya Crosby

и другие.

Nature, Год журнала: 2023, Номер 619(7969), С. 385 - 393

Опубликована: Июль 5, 2023

Abstract The basic helix–loop–helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members 1 . Here we investigate how chromatinized are engaged by two structurally diverse bHLH proteins: the proto-oncogene MYC-MAX circadian factor CLOCK-BMAL1 (refs. 2,3 ). Both bind to preferentially near nucleosomal entry–exit sites. Structural studies with engineered or native nucleosome sequences show that triggers release from histones gain access. Atop H2A–H2B acidic patch 4 , Per-Arnt-Sim (PAS) dimerization domains engage histone octamer disc. Binding tandem 5–7 at endogenous occurs through direct interactions between protomers is important for cycling. At internal E-boxes, leucine zipper can also interact H2B H3, its binding indirectly enhanced OCT4 elsewhere on nucleosome. E-box position type domain jointly determine contact, affinity degree competition cooperativity other nucleosome-bound factors.

Язык: Английский

Процитировано

56