Novel classes bring unique toxicity profiles: PI3K inhibition combined with chemotherapy results in frequent high-grade adverse events, while ADCs show payload-specific toxicities (e.g., neuropathy and cytopenias with vedotin-based agents; diarrhea and neutropenia with topoisomerase I inhibitor payloads like sacituzumab govitecan) [64,128,132]. Here, PIK3CA is linked to neuropathy.