Molecular targeted therapy for cancer has been a research hotspot for decades. AXL is a member of the TAM family with the high-affinity ligand growth arrest-specific protein 6 (GAS6). The Gas6/AXL signalling pathway is associated with tumour cell growth, metastasis, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance, immune regulation and stem cell maintenance. Different therapeutic agents targeting AXL have been developed, typically including small molecule inhibitors, monoclonal antibodies (mAbs), nucleotide aptamers, soluble receptors, and several natural compounds. In this review, we first provide a comprehensive discussion of the structure, function, regulation, and signalling pathways of AXL. Then, we highlight recent strategies for targeting AXL in the treatment of cancer.AXL-targeted drugs, either as single agents or in combination with conventional chemotherapy or other small molecule inhibitors, are likely to improve the survival of many patients. However, future investigations into AXL molecular signalling networks and robust predictive biomarkers are warranted to select patients who could receive clinical benefit and to avoid potential toxicities.

Targeting immune cells or factors are effective for patients with solid tumors. Myeloid-derived suppressor cells (MDSCs) are known to have immunosuppressive functions, and the levels of MDSCs in patients with solid tumor are assumed to have prognostic values. This meta-analysis aimed at evaluating the relationship between MDSCs and the prognosis of patients with solid tumors. We searched articles in PUBMED and EMBASE comprehensively, updated to March 2016. Eight studies with 442 patients were included in the meta-analysis. We analyzed pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). The results showed that MDSCs were associated with poor OS (HR, 1.94; 95% confidence interval [CI], 1.42–2.66; P < 0.0001) in patients with solid tumors. PFS/RFS (HR, 1.85; 95% CI, 1.16–2.97; P = 0.01) also indicated the association between MDSCs and prognosis. The HRs and 95% CIs for OS in Asian and non-Asian patients were 2.53 (95% CI 1.61–3.42, p < 0.00001) and 1.67 (95% CI 1.14–2.46, p < 0.0001), respectively. We further analyzed the data according to tumor types. The combined HRs and 95% CIs for OS were 1.26 (95% CI 1.10–1.44, p = 0.0003) for gastrointestinal (GI) cancer, 2.59 (95% CI 1.69–3.98, p < 0.0001) for hepatocellular carcinoma (HCC) and 1.86 (95% CI 1.26–2.75, p = 0.002) for other tumor types. In conclusion, MDSCs had a fine prognostic value for OS and PFS/RFS in patients with solid tumors. MDSCs could be used as biomarkers to evaluate prognosis in clinical practice.

ObjectivesThe neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) have been proved to affect the prognosis of various types of cancers. However, the prognostic role of NLR and PLR in patients with small-cell lung cancer (SCLC) remains controversial. The objective of this study is to assess the prognostic values of NLR, PLR and other potential prognostic indexes in SCLC patients.ResultsThe optimal cutoff levels were 2.65 for NLR, 125 for PLR and 210 for LDH by ROC curves analysis. Patients in the NLR ≥ 2.65 and LDH ≥ 210 groups were significantly correlated with worse PFS and OS. However, patients in the PLR < 125 group presented longer PFS time than patients in the PLR ≥ 125 group. Multivariate analysis showed that NLR ≥ 2.65 was an independent risk factor for both PFS (HR = 1.38; 95% CI 1.04–1.83; P = 0.027) and OS (HR = 1.35; 95% CI 1.02–1.79; P = 0.039). LDH and the clinical stage were independent prognostic factors for PFS in SCLC patients. LDH, surgery history, thoracic RT and PCI were independent prognostic factors for OS.Materials and Methods320 patients with SCLC were enrolled in this research from 2007 to 2014. Data was acquired through patients’ medical records and follow-ups. Receiver operating curve (ROC) was used to determine the optimal cut-off levels of NLR, PLR and lactate dehydrogenase (LDH). The Kaplan-Meier univariate analysis and multivariate Cox regression analysis were used to evaluate the impact of the NLR, PLR and other potential prognostic factors on overall survival (OS) and progressive-free survival (PFS).ConclusionsPretreatment elevated NLR and LDH were independent factors for poor prognosis in SCLC patients. High PLR was associated with poor PFS, but it was not an independent prognostic factor for PFS and OS.