Background:We evaluated germline single nucleotide polymorphisms (SNPs) for association with overall survival (OS) in pazopanib- or sunitinib-treated patients with advanced renal cell carcinoma (aRCC).Methods:The discovery analysis tested 27 SNPs within 13 genes from a phase III pazopanib trial (N=241, study 1). Suggestive associations were then pursued in two independent datasets: a phase III trial (COMPARZ) comparing pazopanib vs sunitinib (N=729, study 2) and an observational study of sunitinib-treated patients (N=89, study 3).Results:In study 1, four SNPs showed nominally significant association (P≤0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated (P≤0.05) with OS in study 2. Because rs1126647 and rs4073 were highly correlated, only rs1126647 was evaluated in study 3, which also showed association (P≤0.05). In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8 × 10−5; variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15–1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients.Conclusions:Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC. These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies.

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Osteosarcoma is a dominating malignant bone tumor with high mortality due to pulmonary metastases. Furthermore, because of the cancer cell erosion and surgery resection, osteosarcoma always causes bone defects, which means dysfunction and disfigurement are seldom inevitable. Although various advanced treatments (e.g. chemotherapy, immunotherapy, radiotherapy) are coming up, the 5-year survival rate for osteosarcoma with metastases is still dismal. In line with this, the more potent treatments for osteosarcoma are in high demand. Curcumin, a perennial herb, has been reportedly applied in the therapy of various types of tumors via different mechanisms. In vitro, it has also been reported that curcumin can inhibit the proliferation of osteosarcoma cell lines and can be used to repair bone defects. This seems curcumin is a promising candidate in osteosarcoma treatment. However, due to its congenital property like hydrophobicity, and low bioavailability, affecting its anticancer effect, clinical applications of curcumin are highly limited. To enhance its performance in cancer therapies, some synergist approaches with curcumin have emerged. The present review presents some prospective ones (i.e. combinations with immunotherapy, chemotherapeutics, bone tissue engineering, and biomaterials) applied in osteosarcoma treatment. Additionally, with the advancements of photodynamic therapy in cancer therapy, this review also prospects the combination of curcumin with photodynamic therapy in osteosarcoma treatment.