What does “Precision Oncology” mean?
“Precision Oncology” refers to the development of therapies targeting patients’ specific cancer genetics. There are many different genes whose overactivity or absence cause cancer, known as oncogenes or tumor suppressors, respectively. By matching drugs that specifically target the critical defects in a patient’s tumor there is the potential for higher efficacy and safety. By appropriately selecting patients based on their tumor genetics, there is a higher probability of successfully treating patients.
Rain Therapeutics works to identify unique compounds and match their mechanisms to unmet needs in cancer by understanding the specific tumor genetics. With this approach, Rain hopes to be able to provide precision medicine strategies to patients with limited options.
Rain’s Pipeline of Precision Oncology Therapeutics
Rain’s lead program, RAIN-32, targets the mouse double minute 2 (MDM2) protein, a critical regulator of TP53. TP53 is known as the “guardian of the genome.” It functions to regulate the cell cycle and in that role is essential for tumor suppression. However, TP53 can be inactivated by MDM2 when MDM2 is overexpressed by a variety of mechanisms including amplification of the MDM2 gene. Thereby, a targeted strategy against MDM2 is a rational approach for a multitude of tumors exhibiting greater MDM2 levels.
For patients with cancers driven by the ErbB/HER family of genes (including EGFR, HER2, HER3, and HER4), Rain has identified tarloxotinib, a prodrug of a pan-HER inhibitor activated by tumor hypoxia. This unique mechanism of activation and delivery of active drug where it is needed (i.e. the site of the tumor) rather than where it is not wanted (i.e. healthy cells), provides patients a targeted strategy that has the potential to attack the tumor, without the debilitating side effects and dose-limitations of non-targeted therapies.
RAD52 Research Program
Rain is also investigating inhibitors of RAD52 in the DNA damage response (DDR) pathway. Inhibiting RAD52 reflects a synthetic lethal strategy where tumor cells may become overly reliant on RAD52 due to other deficiencies in the DDR pathway such as BRCA1/2 deficiency. Inhibiting RAD52 in these, already DDR impaired, tumor cells has a profound selective impact, whereas it is expected to have only modest effect in normal, healthy cells without a defective DDR network. Synthetic lethal strategies represent an exciting precision oncology strategy for Rain.