Cellular processes are fundamentally controlled at the protein level, and all proteins are produced via translation of messenger RNA (mRNA). Cancer originates through a complex series of events, including primarily via mutations that cause changes to either cellular protein content or function. Exacerbating an already complex situation, there are often multiple unique and simultaneous mutations that shift and evolve over time within patients, thereby changing this protein landscape and behavior.
Translation is a highly regulated cellular process and there are several pathways responsible for the production of proteins from mRNA. One major mechanism is called CAP dependent translation, which catalyzes the production of proteins through the eukaryotic initiation factor 4F (eIF4F) CAP complex (an assembly of several proteins that function to accelerate certain protein synthesis).
Many studies have implicated altered 4F CAP complex behavior in cellular transformation and oncogenesis, with enhanced activity being associated with poor prognosis and therapeutic resistance. Oncogene mRNAs have complex tertiary structure and are particularly dependent on the 4F complex for efficient translation. In turn, oncogenic signaling has been shown to release the brakes on this particular mechanism of protein translation. Therapeutics that restore the rate limiting activity of this complex are anticipated to specifically limit oncogenic translational programming in cancer cells.
PIC Therapeutics is working to translate our Scientific Co-Founder's discoveries into small molecule therapeutics that restore dysregulated protein synthesis in cancer cells by targeting the 4F complex. By selectively modulating a distinct mechanism of protein translation, we believe our precision-based therapeutic approach should reduce oncogene translation while preserving translation of non-oncogenic proteins in an array of cancer types regardless of molecular heterogeneity.