3. Antiangiogenic effects of ASA combination with actual proven therapies
The abnormal tumor vessels leads to inefficient delivery of drugs and oxygen into tumors (Jain et al., 1998). Thus, the normalization of the tumor vasculature by antiangiogenic drugs may reinforce other drugs delivery to further solid tumors, thereby producing an enhancement effect. As targeting angiogenesis is rising a great promise in patients as an antitumor therapy in combination with existing chemotherapies (Ma et al., 2008), we analyze antiangiogenesis properties of coadministration with aspirin.
The previous study has revealed that following coadministration with aspirin therapy, VEGF levels decreased in women with breast cancer relative to levels of receiving Tamoxifen therapy alone (Holmes et al.,2013). Combination therapy of ASA drugs with a VEGF inhibitor block angiogenesis more effectively than either agent alone (Huang et al., 2016). In addition, the administration of aspirin as an adjuvant in combination with Temozolomide, Bevacizumab and Sunitinib showed a synergistic effect on reduce capillary-like tube length in comparison to each exposure alone,in fact aspirin enhanced Temozolomide, Sunitinib and Bevacizumab effect, decreasing significantly Glioblastoma-endothelial cells VEGF-stimulated angiogenesis, especially at the high concentration (Navone et al., 2018). Also, the expression of VEGFR-2, HIF-1α, anti-apoptotic BCL-2 and PI3K/AKT suffered a reduction after combined therapy of Temozolomide, Bevacizumab, Sunitinib and aspirin compared to single-drug treatment (Navone et al., 2018).
5-Fluorouracil (5-FU), a rationally synthesized antitumor agent, is widely used to treat several common malignant tumors, including cancer of the skin, colon and breast (Diasio et al., 1989). The expression of VEGF-A and VEGF-C is significantly reduced in the tumors treated with 5-FU combination with aspirin, and the antitumor effect of 5-FU is synergistically enhanced by aspirin (Zhang et al., 2013). There are three registered clinical trials involved in evaluate the antiangiogenesis efficacy of coadministation aspirin in treating cancers (Table1).