Therapeutic effects of lenvatinib in combination with rAd‑p53 for the treatment of non‑small cell lung cancer

Abstract

The aim of the present study was to analyze the effects of the combined treatment of lenvatinib and adenoviral delivered p53 gene (rAd-p53) on non-small cell lung cancer (NSCLC) cells and a total of 120 patients with NSCLC. The therapeutic effects of gene therapy of rAd-p53 and target therapy of Lenvatinib were investigated in NSCLC patients. The anti-tumor effects of combined treatment of llenvatinib and rAd-p53 was administered orally once-daily in NSCLC patients. Patients with NSCLC were divided into three groups and received lenvatinib (n=40), rAd-p53 (n=40) or combined treatment of lenvatinib and rAd-p53 (n=40) for a total of 30 days. Results showed that p53 was down-regulated and VEGFR, FGFR and PDGFR-β were up-regulated in NSCLC tissues compared to adjacent normal tissues. Combined treatment of Lenvatinib and rAd-p53 markedly inhibited NSCLC cell growth, migration and invasion, and promoted apoptosis compared to either lenvatinib or rAd-p53 alone. The most common treatment-related adverse events included hypertension, diarrhea, nausea, proteinuria and body weight loss. Outcomes indicated that combined treatment of lenvatinib and rAd-p53 markedly inhibited tumor growth compared to lenvatinib and rAd-p53 alone for NSCLC patients. Combined treatment of lenvatinib and rAd-p53 did not exhibit drug accumulation after 30-day treatment. In conclusion, these outcomes indicate that combined treatment of lenvatinib and rAd-p53 may be an efficient therapeutic schedule for the treatment of NSCLC patients.

Lenvatinib induces anticancer activity in gallbladder cancer by targeting AKT

“…A previous study demonstrated that lenvatinib inhibited migration and invasion in non-small cell lung cancer cells [22]. He et al also revealed that lenvatinib inhibited cell migration and invasion in HCC SMMC7721 and Hep3B cells by suppressing the expression of MMP-1, 2, 7, 9, 10 and 16 and increasing the expression of tissue inhibitor of metalloproteinases (TIMP)-1, 3 and 4 [23].…”

Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression

“…Since KRAS alterations are viewed as an old target, the role of KRAS in therapy should be reconsidered [ 38 ]—even more so, as combination therapy has been shown to increase overall and progression-free survival for patients when chemotherapy is not possible [ 39 ]. There is an increasing number of studies that consider the possibility of restoring normal protein function in mutant genes such as KRAS to account for the damaging effects of such mutations [ 40 , 41 , 42 ], particularly as there is increasing proof that co-occurring mutations with KRAS have significant clinical relevance. It has been shown that different KRAS mutation subtypes correlate with different concomitant mutations, such as coexistent KRAS (G12D) substitution with PIK3CA (H1047R), which could promote early KRAS -initiated tumorigenesis [ 43 ].…”

MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis

“…This modest survival benefit may, however, be lost due to drug resistance, as has been observed for Sorafenib [12]. Lenvatinib primarily affects angiogenesis, and additional studies implied that orally administered Lenvatinib exhibited anti-angiogenic activity in thyroid cancer, lung cancer and HCC [8,10,13]. In addition, anti-proliferative effects of Lenvatinib have been observed in different cancer cell types, both in vitro and in vivo [14,15].…”