The heterogeneity of response even in the case of established biomarkers, and unknown frequencies of responders in biomarker negative populations, together with multiple molecular phenotypes conferring response to specific agents (for example, PARP inhibitor responsiveness in tumours with BRCA1, BRCA2, PALB2, and PTEN aberrations) generates significant complexities and challenges in advancing these therapeutic strategies. The gene discussed is PALB2; the disease is neoplasm.