Immune checkpoint blockade is one of the major advances in cancer treatment in recent years. However, the majority of immune checkpoints are embedded in the cell membrane and this fact represents a limitation for targeted degradation using proteolysis-targeting chimeras (PROTACs).

Aromatase inhibitors (AI) are among the most widely used therapies in the treatment of breast tumors expressing estrogen receptor α (ERα). Alone or in combination with other agents, they are the standard of care for hormone receptor-positive tumors.

The protease mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) is a signaling protein with both molecular scaffolding and protease activity involved in lymphocyte activation. MALT1 is considered a therapeutic target for chronic lymphocytic leukemia (CLL) in patients who develop resistance to Bruton tyrosine kinase (BTK) inhibitors.