Anlotinib Combined With Chemoradiotherapy Exhibits Significant Therapeutic Efficacy in Esophageal Squamous Cell Carcinoma

Abstract

The aim of this study was to evaluate the safety and efficacy of anlotinib combined with chemoradiotherapy for treating esophageal squamous cell carcinoma (ESCC) using patient-derived xenografts (PDXs). Methods: PDX-bearing mice were randomly divided into five groups, as follows: control group receiving normal saline, the group receiving radiotherapy, the group receiving cisplatin combined with radiotherapy, the group receiving anlotinib combined with radiotherapy, and the group receiving anlotinib, and cisplatin combined with radiotherapy. Tumor volumes and body weights were measured three times weekly for 2 weeks. The PDXs were initially assessed by comparing the histology of the original patient tumor tissues with that of the corresponding serially passaged xenografts by hematoxylin and eosin (H&E) and P63 staining. Then, expression of Bax, c-PARP, PCNA, and CD31 was detected using immunohistochemistry, and apoptosis was detected by a TUNEL assay. Cytokines released into plasma were analyzed using protein chip technology. Finally, two case studies of ESCC patients were presented to further verify the results observed in the PDX models. Results: The pathological characteristics of the serially passaged patient tumor-derived xenografts established in our study were in line with those of the original ESCC patient samples. The group receiving anlotinib and cisplatin plus radiotherapy exhibited the strongest antitumor response among the groups. Moreover, the ideal anticancer effects of anlotinib combined with chemoradiotherapy observed in clinical patients were consistent with the results observed in the PDX models, and no serious side effects were observed during treatment. Conclusions: Combination therapy with anlotinib and chemoradiotherapy may be an effective regimen for the treatment of advanced ESCC.

Efficacy and Safety of Anlotinib Combined with Liposomal Doxorubicin Followed by Anlotinib Maintenance in Metastatic Soft Tissue Sarcomas

“…Preclinical studies showed that anlotinib and cytotoxic chemotherapy may lead to a synergistic effect, suggesting these drugs may reduce chemotherapy resistance. 13 Considering the modest efficacy and mild toxicity of anlotinib and liposomal doxorubicin for advanced STS, a cohort of patients with advanced STS were treated with anlotinib combined with liposomal doxorubicin followed anlotinib maintenance for survival benefits in three hospitals since 2019. In this study, it aimed to assess the efficacy and safety of anlotinib combined with liposomal doxorubicin followed by anlotinib maintenance monotherapy in patients with metastatic STS.…”

Anlotinib induces tumor blood vessel normalization to strengthen the anticancer effect of radiotherapy on esophageal cancer by inhibiting EphA2

“…In another clinical trail, it has been noticed that combined administration of nivolumab and Anlotinib as a second-line therapy could improve the physical condition of the patient with advanced ESCC [20]. In addition to that, a recent report has highlighted that anlotinib and chemoradiotherapy in combination has the ideal an-tumor effect to treat ESCC in mice [10]. Not only limited to EC, treatment of Anlotinib works actively in other cancer types.…”

“…In fact, Anlotinib has great therapeutic e cacy in treating cancers, such as advanced non-small cell lung cancer (NSCLC), advanced soft tissue sarcoma and metastatic renal cell carcinoma [9]. In ESCC, it has been reported that Antutinib combined with radiotherapy and chemotherapy has strong anti-tumor effects on patient-derived xenografts bearing mice [10]. In a clinical trail, it has been found that Antutinib combined with chemotherapy could improve the survival of patients with advanced ESCC [11], while Antutinib's treatment mechanism for ES still needs further study.…”

NUT Midline Carcinoma as a Primary Lung Tumor Treated With Anlotinib Combined With Palliative Radiotherapy: a Case Report

“…Arotinib have received its rst approval as a thirdline treatment for refractory advanced non-small-cell lung cancer (NSCLC) in May 2018 [14]. Recent studies have demonstrated that anlotinib increases the sensitivity of pulmonary blastoma to chemotherapy in vivo [15]. As we know, activation of the FGFR signaling pathway promotes chemotherapy resistance.…”