Self‐Boosting Programmable Release of Multiple Therapeutic Agents by Activatable Heterodimeric Prodrug‐Enzyme Assembly for Antitumor Therapy DOI Creative Commons
Shanshan Jiang, Bhaskar Gurram,

Junfei Zhu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 12(2)

Published: Nov. 21, 2024

Abstract Endogenous stimuli‐responsive prodrugs, due to their disease lesion specificity and reduced systemic toxicity, have been widely explored for antitumor therapy. However, reactive oxygen species (ROS) as classical endogenous stimuli in the tumor microenvironment (TME) are not enough achieve expected drug release. Herein, a ROS‐activatable heterodimeric prodrug‐loaded enzyme assembly is developed self‐boosting programmable release of multiple therapeutic agents. The prodrug NBS‐TK‐PTX (namely NTP) composed 5‐(ethylamino)‐9‐diethylaminobenzo[ ]phenothiazinium chloride analog (NBS), paclitaxel (PTX) ROS‐responsive thioketal (TK) linker, which shows strong binding affinity with glucose oxidase (GOx), thus obtaining NTP@GOx assembly. Notably, enzymatic activity GOx inhibited by NTP. achieved following steps: i) partially dissociated acidic TME, releasing small segment NTP GOx. Thereupon, recovered; ii) GOx‐triggered pH reduction further facilitates dissociation NTP@GOx, accelerating large amount release; iii) TK linker cleaved hydrogen peroxide generated catalysis, expediting NBS Type‐I photodynamic therapy PTX chemotherapy, respectively. great potential multimodal synergistic cancer

Language: Английский

DeepTraSynergy: drug combinations using multimodal deep learning with transformers DOI Creative Commons
Fatemeh Rafiei, Hojjat Zeraati, Karim Abbasi

et al.

Bioinformatics, Journal Year: 2023, Volume and Issue: 39(8)

Published: July 19, 2023

Screening bioactive compounds in cancer cell lines receive more attention. Multidisciplinary drugs or drug combinations have a effective role treatments and selectively inhibit the growth of cells.Hence, we propose new deep learning-based approach for combination synergy prediction called DeepTraSynergy. Our proposed utilizes multimodal input including drug-target interaction, protein-protein cell-target interaction to predict synergy. To learn feature representation drugs, utilized transformers. It is worth noting that our multitask predicts three outputs its toxic effect, In approach, main task two other ones are auxiliary tasks help better model. loss functions defined: loss, drug-protein loss. The last designed as losses solution. DeepTraSynergy outperforms classic state-of-the-art models predicting synergistic on latest datasets. algorithm achieves accuracy values 0.7715 0.8052 (an improvement over approaches) DrugCombDB Oncology-Screen datasets, respectively. Also, evaluate contribution each component show effectiveness method. introduction relation between proteins (PPI networks) significantly improves combinations.The source code data available at https://github.com/fatemeh-rafiei/DeepTraSynergy.

Language: Английский

Citations

42
Nanomedicine for autophagy modulation in cancer therapy: a clinical perspective DOI Creative Commons
Tania B. López-Méndez, Miguel Sánchez‐Álvarez, Flavia Trionfetti

et al.

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 4, 2023

Abstract In recent years, progress in nanotechnology provided new tools to treat cancer more effectively. Advances biomaterials tailored for drug delivery have the potential overcome limited selectivity and side effects frequently associated with traditional therapeutic agents. While autophagy is pivotal determining cell fate adaptation different challenges, despite fact that it dysregulated cancer, antitumor strategies leveraging on or targeting this process are scarce. This due many reasons, including very contextual of low bioavailability non-targeted existing modulatory compounds. Conjugating versatile characteristics nanoparticles modulators may render these drugs safer effective treatment. Here, we review current standing questions biology tumor progression, precursory studies state-of-the-art harnessing nanomaterials science enhance specificity modulators.

Language: Английский

Citations

27
m6A RNA methylation orchestrates transcriptional dormancy during paused pluripotency DOI
Évelyne Collignon, Brandon Cho,

Giacomo Furlan

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(9), P. 1279 - 1289

Published: Sept. 1, 2023

Language: Английский

Citations

24
mTOR pathway occupies a central role in the emergence of latent cancer cells DOI Creative Commons
Kseniia V. Aleksandrova, Mikhail L. Vorobev, Irina I. Suvorova

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)

Published: Feb. 28, 2024

Abstract The current focus in oncology research is the translational control of cancer cells as a major mechanism cellular plasticity. Recent evidence has prompted reevaluation role mTOR pathway development leading to new conclusions. mechanistic inhibition well known be tool for generating quiescent stem and cells. In response suppression, dynamically change their proteome, triggering alternative non-canonical translation mechanisms. shift selective may have clinical relevance, since tumor can acquire phenotypical features. This review provides insights into patterns functioning cells, enhancing our understanding biology latent metastasis.

Language: Английский

Citations

12
Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies DOI Creative Commons
Jun He,

Zejing Qiu,

Jingjing Fan

et al.

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

Published: Aug. 14, 2024

Non-genetic mechanisms have recently emerged as important drivers of anticancer drug resistance. Among these, the tolerant persister (DTP) cell phenotype is attracting more and attention giving a predominant non-genetic role in cancer therapy The DTP characterized by quiescent or slow-cell-cycle reversible state subpopulation inert specialization to stimuli, which tolerates exposure some extent through interaction multiple underlying recovering growth proliferation after withdrawal, ultimately leading treatment resistance recurrence. Therefore, targeting cells anticipated provide new opportunities for patients, although our current knowledge these remains limited. In this review, we comprehensive overview formation characteristics cells, investigate potential drugs (including preclinical drugs, novel use old natural products) based on different medicine models, discuss necessity feasibility anti-DTP therapy, related application forms, future issues that will need be addressed advance emerging field towards clinical applications. Nonetheless, understanding functions may enable us develop effective improve outcomes patients.

Language: Английский

Citations

12
Sonocatalytic In Situ Induced Oxygen Storm Precision Enhanced Reactive Oxygen Therapy for Pancreatic Cancer DOI

Meifang Zhang,

Lile Dong,

Li Dong

et al.

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(41)

Published: May 26, 2023

Abstract Deep‐buried tissue, extremely hypoxic blood supply, and complex tumor microenvironment are considered to be the hardest difficult barriers accurate treatment of pancreatic cancer. Herein, a novel Au@Co 3 O 4 (AC)‐polyvinylpyrrolidone (AC‐PVP) sonocatalytic agent radiation sensitizer with multicore–shell structure synthesized by mild reduction method for reshaping special physiological environment Oxygen storms can generated under ultrasonic activation in situ catalyzed H 2 tissue. The oxygen storm improves ability produce superoxide anions sonodynamic therapy as well rapidly supplements oxygen‐dependent on active such auger electrons produced high‐energy ray ionization during radiotherapy (RT), further enhancing efficiency RT. Interestingly, AC‐PVP reduce intracellular glutathione (GSH) level, thus preventing reactive species from being consumed GSH. More importantly, glucose oxidase‐like catalyze tissue , continuously provide substrates form self‐cycling production. This study offers paradigm achieving precise self‐oxygenation overcome barrier cancer efficient synergistic radiotherapy.

Language: Английский

Citations

20
Epstein–Barr Virus Latent Membrane Protein 2A (LMP2A) Enhances ATP Production in B Cell Tumors through mTOR and HIF-1α DOI Open Access

Ryan Incrocci,

Rosalinda Monroy Del Toro,

Grace Devitt

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3944 - 3944

Published: April 2, 2024

Epstein-Barr Virus (EBV) exists in a latent state 90% of the world's population and is linked to numerous cancers, such as Burkitt's Lymphoma, Hodgkin's, non-Hodgkin's Lymphoma. One EBV latency protein, membrane protein 2A (LMP2A), expressed multiple phenotypes. LMP2A signaling has been extensively studied one target mammalian rapamycin (mTOR). Since mTOR reprogramming tumor metabolism increasing levels hypoxia-inducible factor 1 α (HIF-1α), we hypothesized that would increase HIF-1α enhance ATP generation B lymphoma cell lines. Our data indicate increases Burkitt lines were dependent on HIF-1α. Subsequent studies addition inhibitor, rapamycin, blocked LMP2A-dependent Further demonstrate does not by RNA or STAT3 activation. In contrast, mTOR-dependent required phosphorylation p70 S6 Kinase 4E-BP1. These findings implicate importance promoting survival identifying potential pharmaceutical targets treat EBV-associated tumors.

Language: Английский

Citations

5
mTORC2-driven chromatin cGAS mediates chemoresistance through epigenetic reprogramming in colorectal cancer DOI Creative Commons
Guoqing Lv,

Qian Wang,

Lin Lin

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1585 - 1596

Published: July 30, 2024

Abstract Cyclic GMP–AMP synthase (cGAS), a cytosolic DNA sensor that initiates STING-dependent innate immune response, binds tightly to chromatin, where its catalytic activity is inhibited; however, mechanisms underlying cGAS recruitment chromatin and functions of chromatin-bound (ccGAS) remain unclear. Here we show mTORC2-mediated phosphorylation human serine 37 promotes localization in colorectal cancer cells, regulating cell growth drug resistance independently STING. We discovered ccGAS recruits the SWI/SNF complex at specific regions, modifying expression genes linked glutaminolysis replication. Although depletion inhibited growth, it induced chemoresistance fluorouracil treatment vitro vivo. Moreover, blocking kidney-type glutaminase, downstream target, overcame caused by loss. Thus, coordinates plasticity acquired through epigenetic patterning. Targeting both mTORC2–ccGAS glutaminase provides promising strategy eliminate quiescent resistant cells.

Language: Английский

Citations

5
Precision Treatment of Colon Cancer Using Doxorubicin-Loaded Metal–Organic-Framework-Coated Magnetic Nanoparticles DOI Creative Commons
Honglin Jiang, Qing Bao, Tao Yang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(37), P. 49003 - 49012

Published: Sept. 3, 2024

Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed their lack specificity selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe

Language: Английский

Citations

5
Targeting protein synthesis pathways in MYC-amplified medulloblastoma DOI Creative Commons
Devendra Kumar, Ranjana Kanchan, Nagendra K. Chaturvedi

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 8, 2025

Abstract MYC is one of the most deregulated oncogenic transcription factors in human cancers. amplification/or overexpression common Group 3 medulloblastoma and positively associated with poor prognosis. known to regulate major components protein synthesis (translation) machinery, leading promoted rates tumorigenesis. MTOR signaling-driven widespread various cancers, including medulloblastoma, which can promote stabilization MYC. Indeed, our previous studies demonstrate that key mTOR signaling targets, are overexpressed activated MYC-amplified confirming MYC-dependent addiction enhanced medulloblastoma. Further, targeting this pathway combined inhibition translation by small-molecule inhibitors, demonstrates preclinical synergistic anti-tumor potential against MYC-driven vitro vivo. Thus, inhibiting indirectly pathways together may present a highly appropriate strategy for treating other MYC-addicted Evidence strongly proposes MYC/mTOR-driven tumorigenic predominantly control translational machinery elicit cooperative effects on increased cell proliferation, cycle progression, genome dysregulation as mechanism cancer initiation. Several small molecule inhibitors have been developed used clinically immunosuppressants chemotherapy multiple Only few them investigated treatments pediatric tumors. This review explores concurrent Based existing evidence, produces functional synergy could be basis effective therapies

Language: Английский

Citations

0