Acute myeloid leukemia (AML) is a hematological cancer with limited treatment options and characterized by frequent relapse and poor prognosis. The only approved antibody-drug conjugate for AML is gemtuzumab ozogamicin, which targets CD33.
Receptor-interacting protein kinase 1 (RIPK1) helps promote the survival of cancer cells, and degrading it can sensitize tumors to immunotherapy against PD-1. Degrading the entire protein seems to be essential: merely blocking its kinase activity does not sensitize tumors.
Triple-negative breast cancer (TNBC) is a highly aggressive subtype affecting 15%-20% of breast cancer patients. TNBC patients harboring breast cancer susceptibility gene 1/2 (BRCA1/2) mutations have shown improved therapeutic response to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi).