Pre‐clinically, administration of nortriptyline (Nor) blocks the interaction of HOXA1 with PITX2, and suppresses the lysosomal exocytosis, tumor formation, and aggressive behavior, underscoring the functions of HOXA1/PITX2 axis in lysosomal exocytosis‐mediated SASP and cancer progression. Here, PITX2 is linked to cancer.