Anlotinib: A Novel Targeted Drug for Bone and Soft Tissue Sarcoma

Abstract

Bone and soft tissue sarcomas account for approximately 15% of pediatric solid malignant tumors and 1% of adult solid malignant tumors. There are over 50 subtypes of sarcomas, each of which is notably heterogeneous and manifested by remarkable phenotypic and morphological variability. Anlotinib is a novel oral tyrosine kinase inhibitor (TKI) targeting c-kit, platelet-derived growth factor receptors, fibroblast growth factor receptor, and vascular endothelial growth factor receptor. In comparison with the placebo, anlotinib was associated with better overall survival and progression-free survival (PFS) in a phase III trial of patients with advanced non-small cell lung cancer (NSCLC), albeit with cancer progression after two previous lines of treatment. Recently, the National Medical Products Administration approved anlotinib monotherapy as a third-line treatment for patients with advanced NSCLC. Additionally, a phase IIB randomized trial substantiated that anlotinib is associated with a significant longer median PFS in patients with advanced soft tissue sarcoma. Moreover, anlotinib is also effective in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma. Anlotinib has similar tolerability to other TKIs targeting vascular endothelial growth factor receptors and other tyrosine kinase-mediated pathways. However, anlotinib has a notably lower rate of side effects ≥grade 3 relative to sunitinib. This review discussed the remarkable characteristics and major dilemmas of anlotinib as a targeted therapy for sarcomas.

Anlotinib combined with temozolomide suppresses glioblastoma growth via mediation of JAK2/STAT3 signaling pathway

“…With anlotinib treatment, intrahepatic cholangiocarcinoma was inhibited by blocking the VEGFR2/phosphoinositide 3-kinase (PI3K)/Akt cascade. Other cancers shown to be inhibited by anlotinib have included soft tissue sarcoma [ 30 ], esophageal squamous cell carcinoma [ 31 ], and gastric cancer [ 32 ]. Interestingly, the mechanism of anlotinib appears to be different compared to more commonly used anti-angiogenesis drugs.…”

Application of Anlotinib Combined With Neoadjuvant Chemotherapy in Primary EWS/PNET of Lung: A Case Report

“…It is conformed that anlotinib has satisfactory membrane permeability and absorption rates from drug preparation studies ( 9 ). The adverse events (AEs) of anlotinib were appeared in the different kinds of studies, however, most of the incidence were controllable, including hypertension, proteinuria, hand–foot skin reaction, hypothyroidism, elevated alanine aminotransferase, elevated aspartate transaminase, elevated total bilirubin, elevated triglyceride, etc ( 9 , 10 ).…”

“…Anlotinib is a novel oral small molecular ereceptor tyrosine kinase inhibitor that targets VEGFR1, VEGFR3, VEGFR2/KDR, PDGFRA,C-kit and FGFRs ( 9 ). The recent studies showed that the combination of chemotherapy and anlotinib significantly improved survival and was well tolerated in patients with advanced/metastatic STS ( 10 ). We herein reports a case of PPES treated with anrotinib combined with neoadjuvant chemotherapy and postoperative maintenance.…”

Association Between Obesity and Poor Prognosis in Patients Receiving Anlotinib for Advanced Non-Small Cell Lung Cancer

“…The deteriorated dyslipidemia caused by anlotinib might provide an explanation for the poor prognosis of the patients in the obesity group. The elimination half-life (t1/2) of anlotinib was considerably longer than other tyrosine kinase inhibitors ( Li, 2021 ). Previous studies have reported that the decreased mRNA expression and activity of the main metabolic enzymes of anlotinib are found in obese individuals ( Morrish et al, 2011 ; Zhong et al, 2018 ).…”