Fitoterapia, Journal Year: 2022, Volume and Issue: 162, P. 105278 - 105278
Published: Aug. 12, 2022
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: Feb. 6, 2025
Abstract Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% liver and is primarily linked to factors incluidng aflatoxin, hepatitis B (HBV) C (HCV), metabolic disorders. There are no obvious symptoms in early stage HCC, which often leads delays diagnosis. Therefore, HCC patients usually present tumors advanced incurable stages. Several signaling pathways dis-regulated cause uncontrolled cell propagation, metastasis, recurrence HCC. Beyond frequently altered therapeutically targeted receptor tyrosine kinase (RTK) involved differentiation, telomere regulation, epigenetic modification stress response also provide therapeutic potential. Investigating key their inhibitors pivotal for achieving advancements management At present, primary approaches (TKI), immune checkpoint (ICI), combination regimens. New trials investigating therapies involving ICIs TKIs or anti-VEGF (endothelial growth factor) therapies, as well combinations two immunotherapy The outcomes these expected revolutionize across all Here, we here comprehensive review cellular pathways, potential, evidence derived from late-stage clinical discuss concepts underlying earlier trials, biomarker identification, development more effective therapeutics
Language: Английский
Citations
10
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189310 - 189310
Published: April 1, 2025
Language: Английский
Citations
2
Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14
Published: Feb. 13, 2023
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and it usually occurs following chronic disease. Although some progress has been made in treatment HCC, prognosis patients with advanced HCC not optimistic, mainly because inevitable development drug resistance. Therefore, multi-target kinase inhibitors for such as sorafenib, lenvatinib, cabozantinib, regorafenib, produce small clinical benefits HCC. It necessary to study mechanism inhibitor resistance explore possible solutions overcome this improve benefits. In study, we reviewed mechanisms discussed strategies that can be used outcomes.
Language: Английский
Citations
31
Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(8), P. 2130 - 2130
Published: Aug. 14, 2023
Hepatocellular carcinoma (HCC) poses a significant global health concern, with its incidence steadily increasing. The development of HCC is multifaceted, multi-step process involving alterations in various signaling cascades. In recent years, progress has been made understanding the molecular pathways that play central roles hepatocarcinogenesis. particular, EGFR/PI3K/AKT/mTOR pathway garnered renewed attention from both basic and clinical researchers. Preclinical studies vitro vivo have shown effectiveness targeting key components this human cells. Thus, these small molecule inhibitors holds promise as potential therapeutic option for patients HCC. review, we explore advancements role assess cascade strategy therapy based on preclinical studies.
Language: Английский
Citations
28
Liver International, Journal Year: 2024, Volume and Issue: 44(8), P. 1808 - 1831
Published: May 3, 2024
Hepatocellular carcinoma (HCC), one of the most prevalent and destructive causes cancer-related deaths worldwide, approximately 70% patients with HCC exhibit advanced disease at diagnosis, limiting potential for radical treatment. For such patients, lenvatinib, a long-awaited alternative to sorafenib first-line targeted therapy, has become key Unfortunately, despite some progress, prognosis remains poor because drug resistance development. However, molecular mechanisms underlying lenvatinib ways relief in are largely unknown lack systematic summary; thus, this review not only aims explore factors contributing HCC, but more importantly, summary methods conquer or mitigate resistance. The results suggest that abnormal activation pathways, transport, epigenetics, tumour microenvironment, cancer stem cells, regulated cell death, epithelial-mesenchymal transition, other involved development subsequent progression. To improve therapeutic outcomes inhibiting acquired resistance, combined therapies, nano-delivery carriers may be possible approaches.
Language: Английский
Citations
15
British Journal of Pharmacology, Journal Year: 2023, Volume and Issue: unknown
Published: Sept. 8, 2023
Tumour angiogenesis is the formation of new blood vessels to support growth a tumour. This process critical for tumour progression and metastasis, making it an attractive approach cancer therapy. Natural products derived from plants, animals or microorganisms exert anti-angiogenic properties can be used inhibit progression. In this review, we comprehensively report on current status natural against four perspectives until March 2023: (1) role pro-angiogenic factors antiangiogenic in angiogenesis; (2) development anti-tumour therapy (monoclonal antibodies, VEGFR-targeted small molecules fusion proteins); (3) summary agents, including polyphenols, polysaccharides, alkaloids, terpenoids, saponins their mechanisms action, (4) future (bioavailability improvement, testing dosage side effects, combination use discovery unique natural-based compounds). Our review aims better understand potential drug inhibiting further aid effective transition these outcomes into clinical trials.
Language: Английский
Citations
23
Medical Oncology, Journal Year: 2024, Volume and Issue: 41(3)
Published: Feb. 21, 2024
Language: Английский
Citations
8
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: Dec. 21, 2024
Lenvatinib is a multi-target tyrosine kinase inhibitor widely used in the treatment of hepatocellular carcinoma (HCC). Its primary mechanism action involves inhibiting signal pathways such as vascular endothelial growth factor receptors (VEGFR) and fibroblast (FGFR), thereby reducing tumor cell proliferation angiogenesis affecting tumor's immune microenvironment. In liver cancer, although lenvatinib monotherapy has shown good clinical effect, problem drug resistance becoming more serious. This may be caused by variety factors, including genetic mutations, signaling pathway remodeling, changes order to overcome resistance, combination other therapeutic strategies gradually become research hotspot, it worth noting that checkpoint inhibitors (ICIs) application prospect. not only enhances anti-tumor response but also helps improve efficacy. However, therapy faces challenges regarding safety tolerability. Therefore, studying mechanisms identifying relevant biomarkers particularly important, aids early diagnosis personalized treatment. article reviews treating efficacy its with inhibitors, causes exploration biomarkers, novel for lenvatinib. We hope provide insights into use scientific settings, offering new cancer.
Language: Английский
Citations
7
Current Cancer Drug Targets, Journal Year: 2022, Volume and Issue: 22(11), P. 865 - 878
Published: April 30, 2022
Lenvatinib is a multikinase inhibitor which mainly hinders liver cancer proliferation by inhibiting angiogenesis. In 2018, was approved for the first-line treatment of patients with advanced hepatocellular carcinoma [HCC] in United States, European Union, Japan, and China. has been established as sorafenib replacement drug higher objective response rate [ORR], longer progression-free survival [PFS], time to progression [TTP]. resistance during become increasingly common recent years. Accordingly, it necessary determine factors associated explore solutions. this review, we sought mechanisms methods reduce summarized achievements treatment.
Language: Английский
Citations
28
Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12
Published: Sept. 8, 2022
Lenvatinib is the first-line treatment for hepatocellular carcinoma (HCC), most common type of primary liver cancer; however, some patients become refractory to lenvatinib. The underlying mechanism lenvatinib resistance (LR) in with advanced HCC remains unclear. We focused on exploring potential LR and novel treatments lenvatinib-resistant HCC. In particular, we established a Huh7 cell line performed vitro, bioinformatic, biochemical assays. Additionally, used Huh7-LR cell-derived xenograft mouse model confirm results vivo. Following induction, multidrug protein 1 (MDR1) breast cancer (BCRP) transporters were markedly upregulated, epidermal growth factor receptor (EGFR), MEK/ERK, PI3K/AKT pathways activated. co-administration elacridar, dual MDR1 BCRP inhibitor, inhibited proliferation induced apoptosis cells. These effects might be due inhibiting stem-like cells (CSCs) properties, by decreasing colony formation downregulating CD133, EpCAM, SOX-9, c-Myc expression. Moreover, gefitinib, an EGFR retarded similar caused inhibition EGFR-mediated MEK/ERK pathway activation. vivo, elacridar or gefitinib suppressed tumour angiogenesis. Therefore, targeting EGFR/PI3K overcome Notably, should treat after induction owing its role Our findings could help develop effective strategies
Language: Английский
Citations
28