Elucidation and therapeutic application of the receptor family of S100A8/A9 that controls cancer sensing mechanism of its transition to destination organ

Abstract

Metastasis, a process in which cancer cells disseminate around the body from the initial disease site, is perhaps the single most critical determiner in assessing the prognosis for a cancer patient. Due to the propensity for the cancer to then spread and invade other tissues, patients whose cancer has metastasised have a much lower survival rate, with nearly 50 per cent of patients dying within five years. Due to its malignant characteristics, metastasis is considered to be one of the most problematic processes in cancer management and therapeutics, often requiring alternative approaches to control and regulate it. Metastatic behaviour varies depending on the type of tissue from which the cancer originates, and metastatic cancer cells often show a preference for particular target tissues to invade. This phenomenon – the ‘seed and soil’ theory – has been extensively reported in oncological studies and describes how the cancer cell ‘seeds’ grow faster in certain ‘soils’ or tissues. The author and his team seek to develop a neutralising antibody and decoy for the S100A8/A9 receptor family, as an extension of the original project. Further profiling and study of the significance of S100A8/A9 and its receptors in other cancer mechanisms will continue until March 2018, after which Sakaguchi will collaborate with experts in therapeutic proteins assessment and preparation consider exploring therapeutic options. ‘We will propose plans based on our achievements and studies so far, and hope to design neutralising and diagnostic antibodies, such as organ-specific SSSRs, extracellular domain-Fc fusion proteins, for all 20 kinds of S100 proteins,’ reveals Sakaguchi. ‘We have already developed the methods to produce functional antibodies to S100 proteins and assessments of the effects of antibody on organ-specific metastasis inhibition. From these studies, we will next turn the antibody into human chimera antibodies for clinical application,’