TY - JOUR
T1 - PARP Inhibitors Resistance: Mechanisms and Perspectives
AU - Giudice, Elena
AU - Gentile, Marica
AU - Salutari, Vanda
AU - Ricci, Caterina
AU - Musacchio, Lucia
AU - Carbone, Maria Vittoria
AU - Ghizzoni, Viola
AU - Camarda, Floriana
AU - Tronconi, Francesca
AU - Nero, Camilla
AU - Ciccarone, Francesca
AU - Scambia, Giovanni
AU - Lorusso, Domenica
PY - 2022
Y1 - 2022
N2 - Simple Summary This review aims to analyze the emerging issue regarding PARP inhibitor's resistance in tumors and their consequence on disease prognosis and treatment. Besides, we evaluate possible strategies and new therapeutic approaches to overcome PARPis resistance. PolyADP-ribose polymerase (PARP) inhibitors (PARPis) represent the first clinically approved drugs able to provoke "synthetic lethality" in patients with homologous recombination-deficient (HRD) tumors. Four PARPis have just received approval for the treatment of several types of cancer. Besides, another three additional PARPis underlying the same mechanism of action are currently under investigation. Despite the success of these targeted agents, the increasing use of PARPis in clinical practice for the treatment of different tumors raised the issue of PARPis resistance, and the consequent disease relapse and dismal prognosis for patients. Several mechanisms of resistance have been investigated, and ongoing studies are currently focusing on strategies to address this challenge and overcome PARPis resistance. This review aims to analyze the mechanisms underlying PARPis resistance known today and discuss potential therapeutic strategies to overcome these processes of resistance in the future.
AB - Simple Summary This review aims to analyze the emerging issue regarding PARP inhibitor's resistance in tumors and their consequence on disease prognosis and treatment. Besides, we evaluate possible strategies and new therapeutic approaches to overcome PARPis resistance. PolyADP-ribose polymerase (PARP) inhibitors (PARPis) represent the first clinically approved drugs able to provoke "synthetic lethality" in patients with homologous recombination-deficient (HRD) tumors. Four PARPis have just received approval for the treatment of several types of cancer. Besides, another three additional PARPis underlying the same mechanism of action are currently under investigation. Despite the success of these targeted agents, the increasing use of PARPis in clinical practice for the treatment of different tumors raised the issue of PARPis resistance, and the consequent disease relapse and dismal prognosis for patients. Several mechanisms of resistance have been investigated, and ongoing studies are currently focusing on strategies to address this challenge and overcome PARPis resistance. This review aims to analyze the mechanisms underlying PARPis resistance known today and discuss potential therapeutic strategies to overcome these processes of resistance in the future.
KW - BRCA
KW - DNA damage repair
KW - PARP inhibitor resistance
KW - homologous recombination
KW - ovarian cancer
KW - polyADP-ribose polymerase (PARP) inhibitor
KW - replication fork
KW - BRCA
KW - DNA damage repair
KW - PARP inhibitor resistance
KW - homologous recombination
KW - ovarian cancer
KW - polyADP-ribose polymerase (PARP) inhibitor
KW - replication fork
UR - https://publicatt.unicatt.it/handle/10807/232456
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85133723873&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85133723873&origin=inward
U2 - 10.3390/cancers14061420
DO - 10.3390/cancers14061420
M3 - Article
SN - 2072-6694
VL - 14
SP - 1
EP - 15
JO - Cancers
JF - Cancers
IS - 6
ER -
