PURPOSE: Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer. METHODS: This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety. RESULTS: Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%). CONCLUSION: Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

Purpose: Although many biological processes are involved in the modification of N⁶-methyladenosine (m⁶A), the exact role of m⁶A in the development of malignant tumors remains unclear. Methyltransferase 3 (METTL3) is a major RNA N⁶-methyladenosine methyltransferase. We aimed to explore the role of METTL3 in colorectal cancer (CRC) carcinogenesis and disease progression. Methods: In this study, immunohistochemistry was performed with a tissue microarray. qRT-PCR and Western blots were used to evaluate the expression of METTL3 in CRC cells. The effect of METTL3 on cell proliferation, migration and invasion of CRC cells was examined by IncuCyte Live Cell Analysis System and transwell assay, respectively. Results: The results suggested that positive expression of METTL3 was significantly associated with longer survival time (P=0.011). We next demonstrated that overexpression of METTL3 could inhibit proliferation, migration and invasion in CRC cells, while downregulation of METTL3 shows the opposite result. Furthermore, downregulation of METTL3 resulted in activation of p-p38 and p-ERK. Moreover, the inhibitors of p38 or ERK kinase could significantly reverse the effect of migration and invasion, which was induced by knockdown of METTL3. Conclusion: We concluded that METTL3 played a tumor-suppressive role in CRC cell proliferation, migration and invasion through p38/ERK pathways, which indicated that METTL3 might be a novel marker for CRC carcinogenesis, progression and survival.