Masitinib in oncology

In oncology, masitinib is being developed in combination with chemotherapies for treatment of malignancies via its immunotherapeutic properties. There is a growing body of scientific knowledge regarding the role of mast cells and macrophages in tumor progression of various cancers. Throughout the process of tumorigenesis, disease progression, and metastasis, the microenvironment of the local host tissue is an active participant and determines the extent of cancer cell proliferation, angiogenesis, invasion, and survival.

There is evidence that increased mast cell activity within the tumor microenvironment can promote disease progression via release of numerous pro-tumoral mediators, down-regulate the immune response to tumors, and modulation of macrophages towards a pro-tumoral state.

Masitinib’s highly selective inhibition of mast cell activation is expected to be of therapeutic benefit by impacting on mast cell related remodeling of the tumor microenvironment.

Evidence indicates that recruitment of inflammatory cells facilitates the growth and spread of some cancers, including prostate cancer, by producing molecules that enhance tumor invasiveness. Indeed, there is a known association between inflammation and advanced prostate cancer development

Mast cells are known to orchestrate inflammatory processes and contribute to the inflammatory cascade by merit of the wide array of pro-inflammatory mediators they release. Moreover, research has demonstrated that mast cells are independent prognostic markers for prostate cancer progression

The potential therapeutic benefit of masitinib in combination with gemcitabine for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC) has been previously reported in preclinical studies, wherein masitinib was shown to enhance the antiproliferative activity of gemcitabine in gemcitabine–refractory pancreatic cancer cell lines¹.

There is a growing body of evidence suggesting that heterogeneity in tumor biology and microenvironment may be an important determinant of survival difference amongst groups of PDAC patients (i.e. aggressive versus relatively slow disease progression, as seen in routine clinical practice), which in turn leads to variability in terms of treatment susceptibility and potential failure of targeted drugs in the overall population. It has been reported that such heterogeneity in PDAC patients may be associated with increased mast cell infiltration into the tumor or tumor microenvironment, both of which are prognostic factors for poor survival in PDAC.

Masitinib is a highly selective inhibitor of mast cell function and activity.

References

1. Humbert M, et al. Masitinib combined with standard gemcitabine chemotherapy: In vitro and in vivo studies in Human Pancreatic Tumour Cell Lines and Ectopic Mouse Model. PLoS ONE. 2010; 5(3): e9430.