Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies

Abstract

Digestive system malignancies are one of the primary causes of cancer-related death. Meanwhile, angiogenesis has been proved to play an important role in the process of cancer neovascularization. Apatinib, a novel targeted antiangiogenic molecule, could generate highly selective competition in the vascular endothelial growth factor receptor-2, involved in tumor progression and metastasis. It has been implied as a promising cancer treatment agent that can prevent tumor cell proliferation meanwhile inhibit tumor angiogenesis. Furthermore, completed clinical trials demonstrated that apatinib could prolong the progression-free survival and overall survival in advanced gastric cancer and primary liver cancer. Recent studies revealed that apatinib had a synergistic effect with immunotherapy as a second-line and third-line treatment regimen for some other cancers. In this review, we summarize the pharmacological properties of apatinib and the latest clinical application in chemotherapy-refractory patients with advanced digestive system cancer. Based on the comparable survival results, the molecular mechanisms of apatinib are prospective to include the antiangiogenic, apoptosis-inducing, and autophagy-inducing properties in the corresponding signaling pathway. Treatment of apatinib monotherapy or combination immunotherapy remains the optimal option for patients with digestive system malignancies in the future.

Apatinib combined with an anti-PD-1 agent promotes antitumour immunity in mice with ovarian cancer

“…Our study showed that the three experimental groups promoted the in ltration of CD4 + and CD8 + T cells into the TME with varying degree, and the in ltration of CD4 + and CD8 + T cells in the combination therapy group was greater than that in the other groups. Similar results have been reported in digestive system malignancies [32]. CD8 + T cells interrupt angiogenesis by secreting IFN-γ [25].…”

Efficacy and safety of tyrosine kinase inhibitors for advanced metastatic thyroid cancer: A systematic review and network meta-analysis of randomized controlled trials

“…[28] In previous studies, apatinib was shown to have an effect on human patients who had received chemotherapy for thyroid cancer and other advanced cancers, such as gastric cancer (6.5 vs 4.7 months, P = .0149), liver cancer, colorectal cancer, and breast cancer. [29][30][31][32] It can effectively exert antitumor effects. Previous clinical studies have shown that apatinib is a viable treatment option for advanced thyroid cancer with significant efficacy in ORR, PFS, and OS, and a good safety profile.…”

Apatinib plus docetaxel or pemetrexed shows promising activities against non-small cell lung cancer with brain metastasis: a retrospective analysis

“…Originally, apatinib was regarded as an anti-angiogenesis inhibitor against VEGFR-2, similar to drugs of a similar type, namely, sorafenib, sunitinib, and cabozantinib ( 31 ). Considering the limited efficiency of other anti-angiogenesis inhibitors, such as cediranib ( 32 ) in advanced NSCLC, it is rather possible that mechanism of apatinib may be different ( 33 ). Apatinib may also possess other targets, such as RET, FlT3, and so on ( 34 ).…”