RNA helicase mechanism is key to all the cells, especially to the proliferating cells that need higher protein synthesis like cancer cells. Most of the pathways hyper activated by the major oncogenes are influenced by mechanisms and pathways mediated by DDX helicase showing how DDX helicase is actively involved in tumor pathogenesis. That is why it is no surprise that our DDX inhibitor compounds are active against several types of tumors, bearing different mutations as well as arising in different organs. It remains one of our main objective and interest to investigate if there are any characteristics that might render the tumors more or less sensitive to the compounds, including oncogene mutations or cell type, that will support clinical development of a therapy, in terms of patient selection and stratification for clinical studies, as well as synthetic lethality and combinations approach.
Lung cancer and liver cancer
FHP compounds have shown to be active against several forms of cancer, both in vitro and in vivo. Even though the data collected so far have shown broad-spectrum activity of these compounds against mechanisms which are common to all cancer cells, FHP has decided to focus on two of the most difficult-to cure types of cancer: lung cancer and liver cancer. The choice to focus mainly on these two types of cancer for the clinical development was inducted by the fact that there are very few therapeutic possibilities and a high frequency of therapy resistance for these types of tumors. Especially for the lung cancer, we are already considering to extend the immortalized and primary cell lines’ group to cover a significant number of mutations and cancer subtypes and obtain data translatable to the patients on which we can further test our compounds. Other imminent projects include some in vivo studies in subcutaneous and orthotopic xenograft models as a proof-of-principle. The first in vitro data show activity in the presence of different mutations, and the first in vivo data in subcutaneous xenografts show ability of the compounds to contrast tumor growth without signs of toxicity. Additional in vivo studies are in preparation for Q1-Q2 2021.