Vaccine adjuvants for immunotherapy: type, mechanisms and clinical applications DOI Creative Commons
Nimeet Desai,

Sherrin Gotru,

Sagar Salave

et al.

Frontiers in Biomaterials Science, Journal Year: 2025, Volume and Issue: 4

Published: Feb. 12, 2025

Immunotherapy has emerged as a powerful approach in treating various diseases, yet its success often hinges on the efficacy of adjuvants, agents that boost immune responses to therapeutic targets. Traditional adjuvants have offered foundational support but may fall short achieving specificity and potency required for advanced therapies. This review highlights new generation poised address these limitations. We explore range innovative agents, including non-inflammatory nucleic acid bacterial derivatives, synthetic molecules, which are redefining role immunotherapy. These emerging hold promise enhancing while tailoring therapies specific disease contexts, from cancer infectious diseases. By examining applications potential this aims provide comprehensive understanding how they can advance immunotherapy levels precision. Through development novel stands achieve more targeted sustained impacts, paving way improved outcomes patient care.

Language: Английский

STIMULI-RESPONSIVE SUPRAMOLECULAR HYDROGELS FOR PACLITAXEL DELIVERY: PROGRESS AND PROSPECTS DOI Creative Commons

Mohammad Qutub,

Amol Tatode, Jayshree Taksande

et al.

Aspects of Molecular Medicine, Journal Year: 2025, Volume and Issue: 5, P. 100062 - 100062

Published: Jan. 5, 2025

Citations

6
Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies DOI Creative Commons
Xingyu Wang, Benoı̂t Gigant,

Xi Zheng

et al.

MedComm – Oncology, Journal Year: 2023, Volume and Issue: 2(3)

Published: Aug. 16, 2023

Abstract Microtubules are pivotal in diverse cellular functions encompassing cell signaling, morphology, intracellular trafficking, and mitosis/division. They validated targets for disease treatment, notably hematological cancers solid tumors. Microtubule‐targeting agents (MTAs) exert their effects by modulating microtubule dynamics, impeding proliferation, promoting death. Recent advances structural biology have unveiled novel perspectives investigating multiple binding sites mechanisms of action used MTAs. In this review, we first provide an overview the intricate structure dynamics microtubules. Then explore seven three primary strategies (stabilization, destabilization, degradation) harnessed Furthermore, introduce emerging domain microtubule‐targeting degraders, exemplified PROteolysis TArgeting Chimeras small‐molecule which enable precise degradation specific microtubule‐associated proteins implicated cancer pathogenesis. Additionally, discuss promising realm precision‐targeted approaches, including antibody–drug conjugates utilization photopharmacology Lastly, a comprehensive clinical applications therapies, assessing efficacy current challenges. We aim to global picture MTAs development as well insights into drug discovery treatment.

Language: Английский

Citations

32
Targeting TACC3 Induces Immunogenic Cell Death and Enhances T-DM1 Response in HER2-Positive Breast Cancer DOI Creative Commons
Mustafa Emre Gedik, Özge Saatci, Nathaniel Oberholtzer

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(9), P. 1475 - 1490

Published: Feb. 6, 2024

Trastuzumab emtansine (T-DM1) was the first and one of most successful antibody-drug conjugates (ADC) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells, T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form death. The payload mediated ICD by inducing eIF2α phosphorylation, surface exposure calreticulin, ATP HMGB1 release, secretion ICD-related cytokines, all which were lost resistance. Accordingly, gene signatures pretreatment samples correlated with response T-DM1-containing therapy, increased infiltration antitumor CD8+ T cells posttreatment better Transforming acidic coiled-coil containing 3 (TACC3) overexpressed T-DM1-resistant responsive patients had reduced TACC3 protein expression whereas nonresponders exhibited during treatment. Notably, genetic or pharmacologic inhibition restored T-DM1-induced SAC activation induction markers vitro. Finally, vivo elicited a vaccination assay potentiated efficacy dendritic maturation enhancing intratumoral cytotoxic cells. Together, these results illustrate key mechanism action targeting can restore T-DM1-mediated overcome

Language: Английский

Citations

12
Sirtuin dysregulation in Parkinson's disease: Implications of acetylation and deacetylation processes DOI
Sonia Dhiman, Ashi Mannan, Ayushi Taneja

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 342, P. 122537 - 122537

Published: Feb. 29, 2024

Language: Английский

Citations

10
Molecular and Cellular Involvement in CIPN DOI Creative Commons
Housem Kacem, Annamaria Cimini, Michele d’Angelo

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 751 - 751

Published: March 28, 2024

Many anti-cancer drugs, such as taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors, can cause chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a frequent harmful side effect that affects the sensory, motor, autonomic nerves, leading to pain, numbness, tingling, weakness, reduced quality of life. The causes are not fully known, but they involve direct nerve damage, oxidative stress, inflammation, DNA microtubule dysfunction, altered ion channel activity. also affected by genetic, epigenetic, environmental factors modulate risk intensity damage. Currently, there no effective treatments or prevention methods for CIPN, symptom management mostly symptomatic palliative. Therefore, high demand better understanding cellular molecular mechanisms involved in well development new biomarkers therapeutic targets. This review gives an overview current knowledge challenges field focusing on biological underlying this disorder.

Language: Английский

Citations

9
From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies DOI Open Access
Ehsan Gharib, Gilles A. Robichaud

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9463 - 9463

Published: Aug. 30, 2024

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance treatment approaches. This article provides comprehensive review our current understanding CRC epidemiology, risk factors, pathogenesis, management strategies. We also present intricate cellular architecture colonic crypts their roles intestinal homeostasis. carcinogenesis multistep processes are described, covering conventional adenoma-carcinoma sequence, alternative serrated pathways, influential Vogelstein model, which proposes sequential

Language: Английский

Citations

9
TK216 targets microtubules in Ewing sarcoma cells DOI Creative Commons
Juan Manuel Povedano, Vicky Li, Katherine E. Lake

et al.

Cell chemical biology, Journal Year: 2022, Volume and Issue: 29(8), P. 1325 - 1332.e4

Published: July 7, 2022

Ewing sarcoma (EWS) is a pediatric malignancy driven by the EWSR1-FLI1 fusion protein formed chromosomal translocation t(11; 22). The small molecule TK216 was developed as first-in-class direct inhibitor and in phase II clinical trials combination with vincristine for patients EWS. However, exhibits anti-cancer activity against cancer cell lines xenografts that do not express EWSR1-FLI1, mechanism underlying cytotoxicity remains unresolved. We apply forward-genetics screening platform utilizing engineered hypermutation EWS identify recurrent mutations TUBA1B, encoding ⍺-tubulin, prove sufficient to drive resistance TK216. Using reconstituted microtubule (MT) polymerization vitro cell-based chemical probe competition assays, we demonstrate acts an MT destabilizing agent. This work defines of TK216, explains synergy observed vincristine, calls reexamination ongoing

Language: Английский

Citations

37
The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma DOI Open Access
Katia Grillone, Caterina Riillo, Roberta Rocca

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10222 - 10222

Published: Sept. 6, 2022

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility a wider therapeutic index compared vinca alkaloids taxanes. On these bases, new tricyclic compounds, containing ring an isoindole moiety, has been synthetized, among which SIX2G emerged MTA. Several findings highlighted ability some chemotherapeutics induce immunogenic cell death (ICD), is defined by surface translocation Calreticulin (CALR) via dissociation PP1/GADD34 complex. In this regard, we computationally predicted CALR exposure interacting with PP1 RVxF domain. We assessed both potential cytotoxic activity on in vitro models multiple myeloma (MM), incurable hematological malignancy characterized immunosuppressive milieu. found that treatment inhibited viability inducing G2/M phase cycle arrest apoptosis. Moreover, observed increase hallmarks ICD such exposure, ATP release phospho-eIF2α protein level. Through co-culture experiments immune cells, demonstrated (i) CD86 maturation marker dendritic (ii) CD69 activation T (iii) phagocytosis tumor cells following SIX2G, confirming onset cascade. conclusion, our provide framework further development anti-MM agent.

Language: Английский

Citations

31
Design, synthesis, and molecular docking of novel pyrazole-chalcone analogs of lonazolac as 5-LOX, iNOS and tubulin polymerization inhibitors with potential anticancer and anti-inflammatory activities DOI

Asmaa Ahmed,

Mamdouh F. A. Mohamed, Rasha M. Allam

et al.

Bioorganic Chemistry, Journal Year: 2022, Volume and Issue: 129, P. 106171 - 106171

Published: Sept. 22, 2022

Language: Английский

Citations

29
Microtubules and Cell Division: Potential Pharmacological Targets in Cancer Therapy DOI

Jomon Sebastian,

Krishnan Rathinasamy

Current Drug Targets, Journal Year: 2023, Volume and Issue: 24(11), P. 889 - 918

Published: July 31, 2023

Microtubules are a well-known target in cancer chemotherapy because of their critical role cell division. Chromosome segregation during mitosis depends on the establishment mitotic spindle apparatus through microtubule dynamics. The disruption dynamics stabilization or destabilization microtubules results arrest cells. Microtubule-targeted drugs, which interfere with dynamics, inhibit growth cells at phase and induce apoptotic death. principle microtubule-targeted drugs is to reduce disease unchecked proliferation. Many anti-microtubule agents produce significant inhibition widely used as chemotherapeutic for treatment cancer. that interact generally bind one three sites vinblastine site, taxol colchicine site. Colchicine binds interface tubulin heterodimer induces depolymerization microtubules. binding site much sought-after history drug discovery. colchicine-binding inhibitors have been discovered, but use limited due dose-limiting toxicity resistance humans. Combination therapy can be new strategy overcome these drawbacks currently available anticancer drugs. This review discusses significance potential pharmacological stresses necessity finding fight disease.

Language: Английский

Citations

21