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Ongoing efforts are aimed at maximizing the therapeutic benefit of RLT and include retreatment and combination strategies as well as novel \u03b1-emitter\u2013based radiopharmaceuticals. The increasing use of molecular profiling has led to the identification of recurrent canonical alterations in pancreatic NETs, including in\n                      <jats:italic toggle=\"yes\">MEN1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ATRX<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">DAXX<\/jats:italic>\n                      , PI3K\/Akt\/mTOR, and angiogenic signaling pathways, facilitating the development of effective targeted therapies. However, despite the addition of newer targeted therapies to the therapeutic armamentarium, resistance remains inevitable and highlights the need for improved predictive markers to inform therapy sequencing and novel biomarker-selected therapies. In addition, the development of novel therapeutic strategies including SSTR antagonists, nonpeptide drug conjugates, and novel radiopharmaceutical constructs highlights the potential of biomarker-informed therapies in this space. By contrast, treatment options for NECs remain limited, with modest therapeutic benefit of platinum-based chemotherapy. The identification of delta-like ligand 3 (DLL3) as a therapeutic target in high-grade NENs has led to the development of novel targeted therapies such as T-cell engagers, which have demonstrated promising activity in early phase clinical trials. In addition, other DLL3-targeting agents such as antibody-drug conjugates, trispecific engagers, and cellular therapies remain under investigation. 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