PARP7 (TIPARP)

Class

PARP7 inhibitor (atamparib / RBN-2397), immunomodulatory antineoplastic

Pathway

Restores type I interferon signaling, triggering innate and adaptive antitumor immune response

PARP7, also known as TIPARP, is a member of the poly-ADP-ribose polymerase family, but unlike the well-known PARP1 and PARP2 enzymes involved in DNA repair, PARP7 functions as a mono-ADP-ribosyltransferase that acts as a brake on type I interferon signaling, a pathway central to innate immune surveillance. Many tumors upregulate PARP7 to dampen this interferon response, allowing malignant cells to evade detection by the immune system. Small-molecule inhibitors of PARP7 are designed to release this brake, restoring interferon signaling within the tumor microenvironment. The resulting increase in interferon activity can enhance antigen presentation, promote recruitment of immune effector cells, and help bridge innate immune activation to a more durable adaptive antitumor response. Because PARP7 is mechanistically distinct from the DNA-repair PARPs, selective inhibition aims to achieve immune activation without the hematologic toxicities historically associated with PARP1/2 inhibition. This mechanism is of broad interest in oncology, particularly for tumors that have found ways to suppress interferon signaling as an immune evasion strategy, and may be explored alongside other immunomodulatory approaches that rely on stimulating antitumor immunity rather than directly killing cancer cells through cytotoxic or DNA-damaging effects.