Thus, to foster the successful pre-clinical and clinical development of our c-RAF–PDE8A disruptor therapeutic, it is critical that we clearly categorise biomarkers that: (i) elucidate the mechanism(s) associated with PPI disruption, (ii) allow for prediction of treatment sensitive vs. resistant cancer models, and (iii) highlight rational combination therapy strategies that can overcome potential acquired resistance. The gene discussed is PDE8A; the disease is cancer.