Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117598 - 117598
Published: Oct. 28, 2024
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
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15
Published: Feb. 17, 2025
Renal cell carcinoma (RCC) is a common substantive tumor. According to incomplete statistics, RCC incidence accounts for approximately 90% of renal malignant tumors, and the second most prevalent major tumor in genitourinary system, following bladder cancer. Only 10%–15% chemotherapy regimens metastatic (mRCC) are effective, mRCC has high mortality. Drug transporters proteins located on membrane that responsible absorption, distribution, excretion drugs. Lots drug expressed kidneys. Changes carrier function weaken balance, cause disease, or modify effectiveness treatment. The changes expression these during cancer pathology results multi-drug resistance chemotherapy. In treatment RCC, study helps optimize regimens, improve therapeutic effects, reduce side effects. this review, we summarize advances role genesis, progression, RCC.
Language: Английский
Citations
2
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
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
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2805 - 2805
Published: Feb. 1, 2023
Primary liver cancer is the sixth most common and third cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) a major histologic type with poor prognosis owing to difficulty in early detection, chemotherapy resistance, high recurrence rate disease. Despite recent advancements HCC prevention diagnosis, over 50% patients are diagnosed at Barcelona Clinic Liver Cancer Stage B or C. Systemic therapies recommended for unresectable (uHCC) vascular invasion, extrahepatic metastases, intrahepatic lesions that have limited response transcatheter arterial chemoembolization, but treatment outcome tends be unsatisfactory due acquired drug resistance. Elucidation mechanisms underlying resistance systemic appropriate strategies solve this issue will contribute improved outcomes multidisciplinary uHCC. In review, we summarize findings on drugs such as sorafenib, regorafenib, lenvatinib molecularly targeted therapy, focus epigenetic regulation tumor microenvironment outline approaches improve therapeutic advanced HCC.
Language: Английский
Citations
25
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
Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 612 - 612
Published: Feb. 14, 2023
Lenvatinib is a multi-kinase inhibitor approved as first-line treatment for patients with unresectable advanced hepatocellular carcinoma (HCC). However, its response rate unsatisfactory, primarily due to the acquisition of resistance, which limits clinical significance treating HCC. Recent evidence suggests that epidermal growth factor receptor (EGFR) activation can trigger Lenvatinib-resistance; and considered an important therapeutic target in Curcumin, one most studied naturally occurring botanicals robust anti-cancer activity, also reported be potent tyrosine kinase inhibitor. In this study, we hypothesized anti-EGFR potential Curcumin might help overcome resistance We established two Lenvatinib-resistant cells discovered combination exhibited synergistic anti-tumor efficacy resistant HCC cell lines. line previous reports, lines revealed significant EGFR, genomewide transcriptomic profiling analysis identified PI3K-AKT pathway was associated resistance. The dramatically suppressed gene protein expression EGFR-PI3K-AKT pathway, suggesting overcomes via inhibition EGFR. further validated these findings tumor spheroids derived from conclusion, we, first time, report reverses HCC, their has application adjunctive
Language: Английский
Citations
21
Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14
Published: April 20, 2023
Graphical Abstract In this review, we summerized the absorption, distribution, metabolism, excretion of lenvatinib in clinic. The lastest mechanism and potential approches to overcome resistance caused by were supplied.
Language: Английский
Citations
18
Discovery Medicine, Journal Year: 2024, Volume and Issue: 36(180), P. 199 - 199
Published: Jan. 1, 2024
Background: Lenvatinib is an important molecular target drug for the treatment of advanced hepatocellular carcinoma (HCC). However, application targeted therapies HCC also faces some challenges. Cumulative evidence has shown that curcumol a potential anti-HCC drug. Curcumol can be used as chemosensitizer to enhance antitumor effect chemotherapeutic drugs. The purpose our study explore combined with lenvatinib on HCC. Methods: effects or/and Huh 7 cells cell line were examined using counting kit-8 (CCK-8) assay, colony formation and transwell assay. For in vivo investigation, subcutaneous growth was determined in nude mice. Changes autophagy by transmission electron microscope (TEM). Protein levels apoptotic-related factors, epithelial mesenchymal transition (EMT)-related N-cadherin janus tyrosine kinase 2 (JAK2)/signal transducers activators transcription 3 (STAT3) Western blot. Results: In this study, we found or could promote apoptosis vitro inhibit tumors vivo (curcumol group compared control group, p < 0.05). While combination improve promoting inhibiting (combination 0.05). induce more autolysosome detected TEM. Mechanically, increase expression Bcl-2-associated X protein (Bax), E-cadherin, UNC-51-like 1 (ULK), microtubule-associated light chain (LC3B) II/I, whereas it reduced B-cell lymphoma-2 (Bcl-2), JAK2/STAT3 (curcumol Furthermore, Bax, ULK, LC3B Bcl-2, N-cadherin, These findings suggest enhances cells. Conclusion:
Language: Английский
Citations
8
Journal of Hepatocellular Carcinoma, Journal Year: 2024, Volume and Issue: Volume 11, P. 113 - 129
Published: Jan. 1, 2024
Abstract: Hepatocellular carcinoma is the prevailing malignant neoplasm affecting liver, often diagnosed at an advanced stage and associated with unfavorable overall prognosis. Sorafenib Lenvatinib have emerged as first-line therapeutic drugs for hepatocellular carcinoma, improving prognosis these patients. Nevertheless, issue of tyrosine kinase inhibitor (TKI) resistance poses a substantial obstacle in management carcinoma. The pathogenesis advancement exhibit close association metabolic reprogramming, yet attention given to lipid metabolism dysregulation development remains relatively restricted. This review summarizes potential significance research progress dysfunction Targeting holds promising effective strategy overcome drug future. Keywords: metabolism, sorafenib, lenvatinib, targeted
Language: Английский
Citations
6