Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy DOI Creative Commons
Györgyi Műzes, Ferenc Sípos

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1130 - 1130

Published: April 8, 2023

The immune system and autophagy share a functional relationship. Both innate adaptive responses involve and, depending on the disease’s origin pathophysiology, it may have detrimental or positive role autoimmune disorders. As “double-edged sword” in tumors, can either facilitate impede tumor growth. regulatory network that influences progression treatment resistance is dependent cell tissue types stages. connection between autoimmunity carcinogenesis has not been sufficiently explored past studies. crucial mechanism two phenomena, play substantial role, though specifics remain unclear. Several modifiers demonstrated beneficial effects models of disease, emphasizing their therapeutic potential as treatments for function microenvironment cells subject intensive study. objective this review to investigate simultaneous genesis malignancy, shedding light both sides issue. We believe our work will assist organization current understanding field promote additional research urgent topic.

Language: Английский

Hallmarks of cancer resistance DOI Creative Commons
Muhammad Tufail,

Jia-Ju Hu,

Jie Liang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109979 - 109979

Published: May 15, 2024

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized Warburg effect, and dynamic interplay between cells mitochondria. The role stem (CSCs) in treatment resistance regulatory influence non-coding RNAs, such as long RNAs (lncRNAs), microRNAs (miRNAs), circular (circRNAs), are studied. chapter emphasizes future directions, encompassing advancements immunotherapy, strategies to counter adaptive integration artificial intelligence for predictive modeling, identification biomarkers personalized treatment. comprehensive exploration these provides a foundation innovative therapeutic approaches, aiming navigate complex landscape enhance patient outcomes.

Language: Английский

Citations

20
Supramolecular nanodrug targeting CDK4/6 overcomes BAG1 mediated cisplatin resistance in oral squamous cell carcinoma DOI

Borui Zhao,

Xuan Qin, Rui Fu

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 368, P. 623 - 636

Published: March 16, 2024

Language: Английский

Citations

7
Overcoming Cancer Drug Resistance with Nanoparticle Strategies for Key Protein Inhibition DOI Creative Commons

Hyeonji Yoo,

Yeonjin Kim, Jinseong Kim

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(17), P. 3994 - 3994

Published: Aug. 23, 2024

Drug resistance remains a critical barrier in cancer therapy, diminishing the effectiveness of chemotherapeutic, targeted, and immunotherapeutic agents. Overexpression proteins such as B-cell lymphoma 2 (Bcl-2), inhibitor apoptosis (IAPs), protein kinase B (Akt), P-glycoprotein (P-gp) various cancers leads to by inhibiting apoptosis, enhancing cell survival, expelling drugs. Although several inhibitors targeting these have been developed, their clinical use is often hampered systemic toxicity, poor bioavailability, development. Nanoparticle-based drug delivery systems present promising solution improving solubility, stability, targeted delivery. These leverage Enhanced Permeation Retention (EPR) effect accumulate tumor tissues, reducing off-target toxicity increasing therapeutic efficacy. Co-encapsulation strategies involving anticancer drugs within nanoparticles shown potential achieving coordinated pharmacokinetic pharmacodynamic profiles. This review discusses mechanisms resistance, limitations current inhibitors, advantages nanoparticle overcoming challenges. By advancing technologies, we can enhance treatment outcomes move towards more effective therapies.

Language: Английский

Citations

7
Biological activities of fig latex -loaded cellulose acetate/poly(ethylene oxide) nanofiber for potential therapeutics: Anticancer and antioxidant material DOI
Gomaa El Fawal, Sherien E. Sobhy, E. S. E. Hafez

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 270, P. 132176 - 132176

Published: May 13, 2024

Language: Английский

Citations

6
Combined inhibition of Bcl-2 family members and YAP induces synthetic lethality in metastatic gastric cancer with RASA1 and NF2 deficiency DOI Creative Commons

Jong‐Wan Kwon,

Jeong-Seop Oh,

Sang Hyeok Seok

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Sept. 20, 2023

Abstract Background Targetable molecular drivers of gastric cancer (GC) metastasis remain largely unidentified, leading to limited targeted therapy options for advanced GC. We aimed identify and devise corresponding therapeutic strategies. Methods performed an unbiased in vivo genome-wide CRISPR/Cas9 knockout (KO) screening peritoneal dissemination using genetically engineered GC mouse models. Candidate genes were validated through transplantation assays KO cells. analyzed target expression patterns clinical samples immunohistochemistry. The functional contributions studied knockdown, KO, overexpression approaches tumorsphere organoid assays. Small chemical inhibitors against Bcl-2 members YAP tested vitro . Results identified Nf2 Rasa1 as metastasis-suppressing the screening. Clinically, RASA1 mutations along with low NF2 define a distinct subtype metastatic exhibiting aggressive traits. deficiency increased formation by synergistically amplifying Wnt signaling stem cells (CSCs). enhanced Bcl-2-mediated signaling, conferring resistance inhibition CSCs. This was counteracted via synthetic lethality achieved simultaneous Bcl-2. amplified pathway Bcl-xL, contributing stemness. mutation created vulnerability Bcl-xL inhibition, but additional deletion conferred due activation. combined suppressed stemness co-deficiency. Conclusion Our research unveils intricate interplay between family members, which can lead lethality, offering potential strategy overcome drug resistance. Importantly, our findings support personalized medicine approach where targeting Bcl-2, tailored status, could effectively manage

Language: Английский

Citations

15
Anti‐apoptotic protein BCL‐XL as a therapeutic vulnerability in gastric cancer DOI Creative Commons
Yumin Wei, Ping Zhang, Chao Wang

et al.

Animal Models and Experimental Medicine, Journal Year: 2023, Volume and Issue: 6(3), P. 245 - 254

Published: June 1, 2023

New therapeutic targets are needed to improve the outcomes for gastric cancer (GC) patients with advanced disease. Evasion of programmed cell death (apoptosis) is a hallmark cells and direct induction apoptosis by targeting pro-survival BCL2 family proteins represents promising strategy treatment. Therefore, understanding molecular mechanisms underpinning survival could provide basis potential interventions.Here we explored role BCL2L1 encoded anti-apoptotic BCL-XL in GC. Using Droplet Digital PCR (ddPCR) technology investigate DNA amplification GC samples lines, sensitivity lines selective inhibitors A1155463 A1331852, pan-inhibitor ABT-263, VHL-based PROTAC-BCL-XL was analyzed using (CellTiter-Glo) CTG assay vitro. Western Blot (WB) used detect protein expression members manner which kills cells. Co-immunoprecipitation (Co-IP) mechanism A1331852 ABT-263 lines. DDPCR, WB, real-time (RTPCR) were correlation between DNA, RNA, levels, drug activity.The functional showed that subset relies on survival. In more sensitive than pan inhibitor indicating not an optimal BCL-XL. DT2216 appears be active induces time- dose-dependent through proteasome pathway. Statistical analysis level predicts response therapy gene CNVs do reliably predict expression.We identified as target cases high levels expression. Functionally, demonstrated both PROTAC can potently kill reliant However, found copy number variations (CNVs) cannot expression, but serves useful biomarker predicting BCL-XL-targeting compounds. Taken together, our study pinpointed druggable specific subsets

Language: Английский

Citations

11
Bcl-xL targeting eliminates ageing tumor-promoting neutrophils and inhibits lung tumor growth DOI Creative Commons
Anita Bodac,

Abdullah Mayet,

Sarika Rana

et al.

EMBO Molecular Medicine, Journal Year: 2023, Volume and Issue: 16(1), P. 158 - 184

Published: Dec. 20, 2023

Language: Английский

Citations

11
Transitioning to a Personalized Approach in Molecularly Subtyped Small-Cell Lung Cancer (SCLC) DOI Open Access
Anna Grenda, Paweł Krawczyk,

Adrian Obara

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4208 - 4208

Published: April 10, 2024

Lung cancer has become a major public health concern, standing as the leading cause of cancer-related deaths worldwide. Among its subtypes, small-cell lung (SCLC) is characterized by aggressive and rapid growth, poor differentiation, neuroendocrine features. Typically, SCLC diagnosed at an advanced stage (extensive disease, ED-SCLC), with distant metastases, strongly associated tobacco smoking prognosis. Recent clinical trials, such CASPIAN IMpower133, have demonstrated promising outcomes incorporation immune checkpoint inhibitors in first-line chemotherapy, to prolonged progression-free survival overall patients ED-SCLC compared standard chemotherapy. Other studies emphasized potential for future development molecularly targeted therapies patients, including IGF-1R, DLL3, BCL-2, MYC, or PARP. The molecular subdivision based on transcriptomic immunohistochemical analyses represents significant advancement both diagnostic approaches patients. Specific pathways are activated within distinct transcriptome subtypes SCLC, offering personalized treatment strategies, immunotherapies. Such tailored hold promise significantly improving

Language: Английский

Citations

4
Evasion of apoptosis and treatment resistance in squamous cell carcinoma of the head and neck DOI Creative Commons

Ben O’Leary,

Heath D. Skinner, Jonathan D. Schoenfeld

et al.

Cancer Treatment Reviews, Journal Year: 2024, Volume and Issue: 129, P. 102773 - 102773

Published: June 1, 2024

Combinations of surgery, radiotherapy and chemotherapy can eradicate tumors in patients with locally advanced squamous cell carcinoma the head neck (LA SCCHN), but a significant proportion progress, recur, or do not respond to therapy due treatment resistance. The prognosis for these is poor, thus new approaches are needed improve outcomes. Key resistance mechanisms chemoradiotherapy (CRT) LA SCCHN alterations pathways that mediate apoptosis, form programmed death. Targeting dysregulation apoptotic represents rational therapeutic strategy many types cancer, number proteins, including pro-survival B-cell lymphoma 2 family inhibitors apoptosis proteins (IAPs), having been identified as druggable targets. This review discusses by which occurs under physiological conditions, how this process abnormally restrained tumor cells, strategies aimed at re-enabling also considered. In particular, development of, future opportunities for, IAP discussed, light recent encouraging proof-of-concept clinical trial data.

Language: Английский

Citations

4
Venetoclax as a possible chemopreventive agent in adenomatous polyposis: A case report DOI Creative Commons
Cautar El Maimouni, María Daca-Álvarez, Julio Delgado

et al.

Gastroenterología y Hepatología (English Edition), Journal Year: 2025, Volume and Issue: 48(3), P. 502239 - 502239

Published: Feb. 28, 2025

Language: Английский

Citations

0