NLRP3 inflammasome-induced pyroptosis in digestive system tumors DOI Creative Commons

Jiexia Wen,

Bin Xuan,

Yang Liu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 4, 2023

Programmed cell death (PCD) refers to in a manner that depends on specific genes encoding signals or activities. PCD includes apoptosis, pyroptosis, autophagy and necrosis (programmed necrosis). Among these mechanisms, pyroptosis is mediated by the gasdermin family accompanied inflammatory immune responses. When pathogens other danger are detected, cytokine action inflammasomes (cytoplasmic multiprotein complexes) lead pyroptosis. The relationship between cancer complex effect of varies different tissue genetic backgrounds. On one hand, can inhibit tumorigenesis progression; as pro-inflammatory death, promote tumor growth creating microenvironment suitable for growth. Indeed, NLRP3 inflammasome known mediate digestive system tumors, such gastric cancer, pancreatic ductal adenocarcinoma, gallbladder oral squamous carcinoma, esophageal which pyroptosis-induced cellular response inhibits development. same process occurs hepatocellular carcinoma some colorectal cancers. current review summarizes mechanisms pathways outlining involvement inflammasome-mediated tumors.

Language: Английский

Systemic treatment for metastatic colorectal cancer DOI Creative Commons

Wattana Leowattana,

Pathomthep Leowattana,

Tawithep Leowattana

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(10), P. 1569 - 1588

Published: March 14, 2023

Significant progress has been achieved in the treatment of metastatic colorectal cancer (mCRC) patients during last 20 years. There are currently numerous treatments available for first-line mCRC. Sophisticated molecular technologies have developed to reveal novel prognostic and predictive biomarkers CRC. The development next-generation sequencing whole-exome sequencing, which strong new tools discovery facilitate delivery customized treatment, resulted tremendous breakthroughs DNA technology recent appropriate adjuvant mCRC determined by tumor stage, presence high-risk pathologic characteristics, microsatellite instability status, patient age, performance status. Chemotherapy, targeted therapy, immunotherapy main systemic with Despite fact that these choices increased overall survival mCRC, remains optimal individuals non-metastatic disease. being used support our ability practice personalized medicine; practical aspects applying regular clinical practice; evolution chemotherapy, strategies front-line setting all reviewed here.

Language: Английский

Citations

48
Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications DOI Creative Commons
Mateusz Kciuk, Manzar Alam, Nemat Ali

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(13), P. 5246 - 5246

Published: July 6, 2023

Cellular signaling pathways involved in the maintenance of equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited prevention treatment cancer. Epigallocatechin-3-gallate (EGCG) is most abundant phenolic compound found green tea. It has been shown to regulate multiple crucial cellular pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, others. Deregulation abovementioned pathophysiology demonstrated EGCG may exert anti-proliferative, anti-inflammatory, apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical clinical studies suggest used numerous disorders, This review aims summarize existing knowledge regarding biological properties EGCG, especially context cancer prophylaxis.

Language: Английский

Citations

43
Targeting KRAS: from metabolic regulation to cancer treatment DOI Creative Commons
Yanyan Shi, Huiling Zheng, Tianzhen Wang

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 11, 2025

The Kirsten rat sarcoma viral oncogene homolog (KRAS) protein plays a key pathogenic role in oncogenesis, cancer progression, and metastasis. Numerous studies have explored the of metabolic alterations KRAS-driven cancers, providing scientific rationale for targeting metabolism treatment. development KRAS-specific inhibitors has also garnered considerable attention, partly due to challenge acquired treatment resistance. Here, we review reprogramming glucose, glutamine, lipids regulated by oncogenic KRAS, with an emphasis on recent insights into relationship between changes mechanisms driven KRAS mutant related advances targeted therapy. We focus inhibitor discovery strategies colorectal, pancreatic, non-small cell lung cancer, including current clinical trials. Therefore, this provides overview understanding associated mutation therapeutic strategies, aiming facilitate challenges support investigation strategies.

Language: Английский

Citations

4
Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers DOI Open Access
Lindsey Carlsen, Kelsey E. Huntington, Wafik S. El‐Deiry

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(4), P. 1028 - 1028

Published: Feb. 17, 2022

Though early-stage colorectal cancer has a high 5 year survival rate of 65–92% depending on the specific stage, this probability drops to 13% after metastasizes. Frontline treatments for such as chemotherapy and radiation often produce dose-limiting toxicities in patients acquired resistance cells. Additional targeted are needed improve patient outcomes quality life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules engage train immune system kill Preclinical clinical investigations immunotherapy including checkpoint blockade, adoptive cell therapy, monoclonal oncolytic anti-cancer vaccines, modulators have been promising, but demonstrate limitations proficient mismatch repair enzymes. In review, we discuss preclinical studies investigating predictive biomarkers response these treatments. We also consider open questions optimal combination maximize efficacy, minimize toxicity, prevent approaches sensitize repair-proficient immunotherapy.

Language: Английский

Citations

41
PHB2 promotes colorectal cancer cell proliferation and tumorigenesis through NDUFS1-mediated oxidative phosphorylation DOI Creative Commons
Lin Ren, Meng Li, Jing Gao

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 20, 2023

Abstract The alteration of cellular energy metabolism is a hallmark colorectal cancer (CRC). Accumulating evidence has suggested oxidative phosphorylation (OXPHOS) upregulated to meet the demand for in tumor initiation and development. However, role OXPHOS its regulatory mechanism CRC tumorigenesis progression remain unclear. Here, we reveal that Prohibitin 2 (PHB2) expression elevated precancerous adenomas CRC, which promotes cell proliferation CRC. Additionally, knockdown PHB2 significantly reduces mitochondrial levels cells. Meanwhile, NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1), as binding partner, screened identified by co-immunoprecipitation mass spectrometry. Furthermore, directly interacts with NDUFS1 they co-localize mitochondria, facilitates V1 (NDUFV1), regulating activity complex I. Consistently, partial inhibition I also abrogates increased induced overexpression normal human intestinal epithelial cells Collectively, these results indicate stabilize enhance activity, leading levels, thereby promoting Our findings provide new perspective understanding metabolism, well novel intervention strategies therapeutics.

Language: Английский

Citations

39
Erianin inhibits the growth and metastasis through autophagy-dependent ferroptosis in KRASG13D colorectal cancer DOI

Qun Miao,

Wei-Qing Deng,

Wen-Yu Lyu

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 204, P. 301 - 312

Published: May 20, 2023

Language: Английский

Citations

32
Update on Emerging Therapies for Advanced Colorectal Cancer DOI Open Access
Olatunji B. Alese, Christina Wu, William J. Chapin

et al.

American Society of Clinical Oncology Educational Book, Journal Year: 2023, Volume and Issue: 43

Published: May 1, 2023

Colorectal cancer (CRC) is the third most common malignancy worldwide. It projected to increase by 3.2 million new cases and account for 1.6 deaths 2040. Mortality largely due limited treatment options patients who present with advanced disease. Thus, development of effective tolerable therapies crucial. Chemotherapy has been backbone systemic CRC, but utility because invariable resistance therapy, narrow mechanisms action, unfavorable toxicity profile. Tumors that are mismatch repair-deficient have demonstrated remarkable response immune checkpoint inhibitor therapy. However, CRC tumors repair-proficient represent an unmet medical need. Although ERBB2 amplification occurs only in a few cases, it associated left-sided higher incidence brain metastasis. Numerous combinations HER2 inhibitors efficacy, antibody-drug conjugates against innovative strategies this area. The KRAS protein classically considered undruggable. Fortunately, agents targeting G12C mutation paradigm shift management affected could lead advancement drug more mutations. Furthermore, aberrant DNA damage 15%-20% CRCs, emerging poly (ADP-ribose) polymerase (PARP) improve current therapeutic landscape. Multiple novel biomarker-driven approaches reviewed article.

Language: Английский

Citations

27
Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer DOI
Caicun Zhou,

Chongyang Li,

Libo Luo

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(7), P. 1286 - 1300.e8

Published: June 27, 2024

Language: Английский

Citations

15
Signaling pathways in liver cancer: pathogenesis and targeted therapy DOI Creative Commons

Yangtao Xue,

Yeling Ruan,

Yali Wang

et al.

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: May 31, 2024

Abstract Liver cancer remains one of the most prevalent malignancies worldwide with high incidence and mortality rates. Due to its subtle onset, liver is commonly diagnosed at a late stage when surgical interventions are no longer feasible. This situation highlights critical role systemic treatments, including targeted therapies, in bettering patient outcomes. Despite numerous studies on mechanisms underlying cancer, tyrosine kinase inhibitors (TKIs) only widely used clinical inhibitors, represented by sorafenib, whose application greatly limited phenomenon drug resistance. Here we show an in-depth discussion signaling pathways frequently implicated pathogenesis targeting these under investigation or already use management advanced cancer. We elucidate oncogenic roles especially hepatocellular carcinoma (HCC), as well current state research respectively. Given that TKIs represent sole class therapeutics for employed practice, have particularly focused encountered phenomena resistance during HCC treatment. necessitates imperative development innovative strategies urgency overcoming existing limitations. review endeavors shed light utilization therapy vision improve unsatisfactory prognostic outlook those patients.

Language: Английский

Citations

13
Circular RNAs in the KRAS pathway: Emerging players in cancer progression DOI
Md Sadique Hussain, Ehssan Moglad, Muhammad Afzal

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 256, P. 155259 - 155259

Published: March 11, 2024

Language: Английский

Citations

12