Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer DOI Creative Commons
Thomas Cyberski, Alka Singh,

Michael Korzinkin

et al.

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: May 23, 2024

Abstract The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. amplification is consistently observed aggressive forms several solid malignancies correlates with poor prognosis distant metastases. While the tumorigenic effects patients head neck squamous carcinoma (HNSCC) are well known, molecular mechanisms by which this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present unique case patient recurrent/metastatic (R/M) HNSCC who, despite initial response nivolumab-based treatment, developed rapidly progressive metastatic disease after acquisition amplification. We conducted comparative transcriptomic analysis patient’s tumor at baseline upon progression interrogate potential processes through resistance immunotherapy and/or chemoradiation used TCGA-HNSC dataset institutional cohort further explore clinicopathologic features key networks associated HNSCC. This study highlights mechanism inhibitor suggest its use predictive biomarker target R/M

Language: Английский

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

Ming He,

Chao-Guo Cao, Zhihao Ni

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 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.

Language: Английский

Citations

178
Viral vectors and extracellular vesicles: innate delivery systems utilized in CRISPR/Cas-mediated cancer therapy DOI Open Access
Seyed Esmaeil Ahmadi,

Maral Soleymani,

Fahimeh Shahriyary

et al.

Cancer Gene Therapy, Journal Year: 2023, Volume and Issue: 30(7), P. 936 - 954

Published: Feb. 28, 2023

Language: Английский

Citations

52
Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management DOI Creative Commons
Kolawole A. Olofinsan, Heidi Abrahamse, Blassan P. George

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(14), P. 5578 - 5578

Published: July 22, 2023

Cancer is a neoplastic disease that remains global challenge with reported prevalence increasing annually. Though existing drugs can be applied as single or combined therapies for managing this pathology, their concomitant adverse effects in human applications have led to the need continually screen natural products effective and alternative anticancer bioactive principles. Alkaloids are chemical molecules that, due structural diversity, constitute reserve discovery of lead compounds interesting pharmacological activities. Several vitro studies few vivo findings documented various cytotoxic antiproliferative properties alkaloids. This review describes chaetocochin J, neopapillarine, coclaurine, reflexin A, 3,10-dibromofascaplysin neferine, which belong different alkaloid classes antineoplastic been identified recently from plants. Despite low solubility bioavailability, plant-derived alkaloids viable prospects sources antitumor agents. potential achieved if more research on these directed toward investigating ways improving delivery an active form close target cells, preferably no effect neighboring normal tissues.

Language: Английский

Citations

50
Development of long-term primary cell culture of Macrobrachium rosenbergii: morphology, metabolic activity, and cell-cycle analysis DOI Creative Commons

Gurucharan Sudarshan,

Simy Weil,

Rivka Manor

et al.

Frontiers in Marine Science, Journal Year: 2024, Volume and Issue: 10

Published: Jan. 31, 2024

This study describes our attempts to generate a sustainable cell culture of Macrobrachium rosenbergii . We present here continuous longitudinal on the embryonic primary freshwater prawn M. that was uniquely monitored for up 90 days with regard its morphology, metabolic activity, and cell-cycle parameters. The daily monitoring cells’ wellbeing morphology showed seeded cells be changing from attached singular diverse-sized after 4–10 interconnected clusters cells, which apparently increased in number as detected by their density well. Moreover, cultures demonstrated an autonomous transition during 7–10, completely two-dimensional (2D) combination 2D three-dimensional (3D) growing structures, leading formation multilayered spheroid-like masses. activity non-linear elevated pattern peaking day 26, demonstrating proliferation increment retaining statistically significant 40 days, thereafter gradually declining. In parallel, analyses performed through florescence-activated sorting (FACS) G0/G1 S phases were inversely proportional each other. Proliferation, based sustained increase portion arrested phase, 4 24, then decrease between 45 90. Sorting populations 3 24 revealed eight populations, most them expressing putative markers MrMYC MrPCNA , while six expressed also stem-cell MrOct-4 MrSox-2/3 Therefore, assuming reduction distribution toward S, well G2/M, all pointing proliferation, we further hypothesized splitting along experiment at high-proliferating mitotic ratio peaks would enable successful passages. Indeed, culture, succeeded executing two consecutive passages: first 8 second following passage. Cells both passages species-specific Mr18S proliferative After several decades research efforts establish crustacean line—with no published success—here, composed proliferating/stem-cell subpopulations or appearing like clones. These mix-population could serve basic platform immortalization contribute long-term goal establishing cell-culture lines.

Language: Английский

Citations

20
MYC and therapy resistance in cancer: risks and opportunities DOI Creative Commons
Giulio Donati, Bruno Amati

Molecular Oncology, Journal Year: 2022, Volume and Issue: 16(21), P. 3828 - 3854

Published: Oct. 10, 2022

The MYC transcription factor, encoded by the c‐ proto‐oncogene, is activated growth‐promoting signals, and a key regulator of biosynthetic metabolic pathways driving cell growth proliferation. These same processes are deregulated in MYC‐driven tumors, where they become critical for cancer proliferation survival. As other oncogenic insults, overexpressed induces series cellular stresses (metabolic, oxidative, replicative, etc.) collectively known as stress, which impact not only on tumor progression, but also response to therapy, with profound, multifaceted consequences clinical outcome. On one hand, recent evidence uncovered widespread role therapy resistance multiple types, either standard chemotherapeutic or targeted regimens. Reciprocally, imparts molecular dependencies cells, thus giving rise cancer‐specific vulnerabilities that may be exploited obtain synthetic‐lethal interactions novel anticancer drugs. Here we will review current knowledge links between therapeutic responses, discuss possible strategies overcome through new, interventions.

Language: Английский

Citations

56
BRD4 and MYC: power couple in transcription and disease DOI Creative Commons
Aparna Kotekar, Amit Kumar Singh, Ballachanda N. Devaiah

et al.

FEBS Journal, Journal Year: 2022, Volume and Issue: 290(20), P. 4820 - 4842

Published: July 22, 2022

The MYC proto‐oncogene and BRD4, a BET family protein, are two cardinal proteins that have broad influence in cell biology disease. Both expressed ubiquitously mammalian cells play central roles controlling growth, development, stress responses metabolic function. As chromatin transcriptional regulators, they critical role regulating the expression of burgeoning array genes, maintaining architecture genome stability. Consequently, impairment their function or regulation leads to many diseases, with cancer being most predominant. Interestingly, accumulating evidence indicates functions tightly intertwined BRD4 at both post‐transcriptional levels. Here, we review mechanisms by which regulated, governing various molecular consequences dysregulation lead We present perspective how regulatory for could be entwined multiple points BRD4‐MYC nexus modulation disease upon dysregulation.

Language: Английский

Citations

44
MYC function and regulation in physiological perspective DOI Creative Commons
Rajeev Jha, Fedor Kouzine, David Levens

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Oct. 24, 2023

MYC, a key member of the Myc-proto-oncogene family, is universal transcription amplifier that regulates almost every physiological process in cell including cycle, proliferation, metabolism, differentiation, and apoptosis. MYC interacts with several cofactors, chromatin modifiers, regulators to direct gene expression. levels are tightly regulated, deregulation has been associated numerous diseases cancer. Understanding comprehensive biology under conditions an utmost necessity demark biological functions from its pathological functions. Here we review recent advances mechanisms, functions, regulation MYC. We also emphasize role as global amplifier.

Language: Английский

Citations

31
Unlocking the potential of PROTACs: A comprehensive review of protein degradation strategies in disease therapy DOI
Ritesh P. Bhole, Payal R. Kute, Rupesh V. Chikhale

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 139, P. 106720 - 106720

Published: July 13, 2023

Language: Английский

Citations

25
The impact of the BCR-ABL oncogene in the pathology and treatment of chronic myeloid leukemia DOI Creative Commons
Mohamed El‐Tanani, Hamdi Nsairat, Ismail Matalka

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 254, P. 155161 - 155161

Published: Jan. 22, 2024

Chronic Myeloid Leukemia (CML) is characterized by chromosomal aberrations involving the fusion of BCR and ABL genes on chromosome 22, resulting from a reciprocal translocation between chromosomes 9 22. This gives rise to oncogenic BCR-ABL, an aberrant tyrosine kinase identified as Abl protein. The protein intricately regulates cell cycle phosphorylating residues through diverse signaling pathways. In CML, BCR-ABL disrupts first exon Abl, leading sustained activation resistance deactivation mechanisms. Pharmacological interventions, such imatinib, effectively target BCR-ABL's activity binding near active site, disrupting ATP binding, inhibiting downstream phosphorylation. Nevertheless, emergence resistance, often attributed cap structure mutations, poses challenge imatinib efficacy. Current research endeavours are directed towards overcoming investigating innovative therapeutic strategies. article offers comprehensive analysis structural attributes emphasizing its pivotal role biomarker in CML. It underscores imperative for ongoing refine treatment modalities enhance overall outcomes managing

Language: Английский

Citations

15
MYC the oncogene from hell: Novel opportunities for cancer therapy DOI

Adriana Papadimitropoulou,

Maria Makri,

Grigoris Zoidis

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 267, P. 116194 - 116194

Published: Feb. 2, 2024

Language: Английский

Citations

13