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Cervical cancer is one of the most common gynecological tumors, and the majority of early-stage cervical cancer patients achieve good recovery through surgical treatment and concurrent chemoradiotherapy (CCRT). However, for patients with recurrent, persistent, metastatic cervical cancer, effective treatment is rare, except for bevacizumab combined with chemotherapy. Programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors might be a novel choice to improve the clinical outcomes of these patients. Thus far, some pivotal trials, including Keynote 028, Keynote 158 and Checkmate 358, have indicated established clinical benefit of PD-1/PD-L1 inhibitors in cervical cancer. In light of these data, the FDA has approved pembrolizumab for patients with recurrent or metastatic cervical cancer with disease progression during or after chemotherapy. There are also some ongoing studies that may provide more evidence for the PD-1/PD-L1 pathway as a therapeutic target in cervical cancer. In this review, we have summarized the status and application of PD-1/PD-L1 inhibitors in clinical trials for the treatment of cervical cancer and suggested some future directions in this field.

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Vascular endothelial growth factor

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Hypoxic response of endothelial cells (EC) is an important component of tumor angiogenesis. Especially, hypoxiainducible factor-1 (HIF-1) -dependent EC-specific mechanism is an essential component of tumor angiogenesis. Recently, the Rho/Rho-associated kinase (ROCK) signaling has been shown to play a key role in HIF-1A induction in renal cell carcinoma and trophoblast. The present study was designed to investigate whether low oxygen conditions might modulate HIF-1A expression through the Rho/ROCK signaling in human umbilical vascular ECs (HUVEC). Pull-down assay showed that hypoxia stimulated RhoA activity. Under hypoxic conditions, HUVECs transfected with small interfering RNA of RhoA and ROCK2 exhibited decreased levels of HIF-1A protein compared with nontargeted small interfering RNA transfectants, whereas HIF-1A mRNA levels were not altered. One of ROCK inhibitors, fasudil, inhibited hypoxia-induced HIF-1A expression without altering HIF-1A mRNA expression.

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