What co-mutation and pathway patterns drive endocrine resistance beyond ESR1, and which are both druggable and predictive of response to next-gen SERDs like camizestrant?

Which resistance mechanisms after osimertinib create targetable dependencies (e.g., TROP2, HER3), and which modality (ADC vs. bispecific vs. small molecule) is best suited for each biology?

Which inflammatory pathways beyond type 2 (IL-33, innate immunity, infection-driven signals) define COPD subtypes with high unmet need and low biologic competition?

Which molecular and clinical features of ATTR progression (genotype, amyloid burden, cardiac stress markers) define patient segments where TTR silencing provides maximal benefit over stabilizers?

Which metabolic pathways beyond incretins (amylin, glucagon synergy, energy expenditure) drive superior weight loss and cardiometabolic outcomes, and in which patient phenotypes?