TY - JOUR
T1 - Potential Targeted Therapies in Ovarian Cancer
AU - Sisman, Yagmur
AU - Vestergaard, Lau Kræsing
AU - de Oliveira, Douglas Nogueira Perez
AU - Poulsen, Tim Svenstrup
AU - Schnack, Tine Henrichsen
AU - Høgdall, Claus
AU - Høgdall, Estrid
PY - 2022/10/26
Y1 - 2022/10/26
N2 - BACKGROUND: We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian cancer (HGSC).METHODS: We characterized the mutational profile of 128 HGSC patients. Clinical data were obtained from the Danish Gynecological Database and tissue samples were collected through the Danish CancerBiobank. DNA was analyzed using NGS.RESULTS: 47 (37%) patients were platinum-sensitive, 32 (25%) partially platinum-sensitive, 35 (27%) platinum-resistant, and three (2%) platinum-refractory, while 11 (9%) patients did not receive chemotherapy. Overall, 27 (21%) had known druggable targets. Twelve (26%) platinum-sensitive patients had druggable targets for PARP inhibitors: one for tyrosine kinase inhibitors and one for immunotherapy treatment. Eight (25%) partially platinum-sensitive patients had druggable targets: seven were eligible for PARP inhibitors and one was potentially eligible for alpesilib and hormone therapy. Seven (20%) platinum-resistant patients had druggable targets: six (86%) were potentially eligible for PARP inhibitors, one for immunotherapy, and one for erdafitinib.CONCLUSIONS: PARP inhibitors are the most frequent potential targeted therapy in HGSC. However, other targeted therapies remain relevant for investigation according to our mutational findings.
AB - BACKGROUND: We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian cancer (HGSC).METHODS: We characterized the mutational profile of 128 HGSC patients. Clinical data were obtained from the Danish Gynecological Database and tissue samples were collected through the Danish CancerBiobank. DNA was analyzed using NGS.RESULTS: 47 (37%) patients were platinum-sensitive, 32 (25%) partially platinum-sensitive, 35 (27%) platinum-resistant, and three (2%) platinum-refractory, while 11 (9%) patients did not receive chemotherapy. Overall, 27 (21%) had known druggable targets. Twelve (26%) platinum-sensitive patients had druggable targets for PARP inhibitors: one for tyrosine kinase inhibitors and one for immunotherapy treatment. Eight (25%) partially platinum-sensitive patients had druggable targets: seven were eligible for PARP inhibitors and one was potentially eligible for alpesilib and hormone therapy. Seven (20%) platinum-resistant patients had druggable targets: six (86%) were potentially eligible for PARP inhibitors, one for immunotherapy, and one for erdafitinib.CONCLUSIONS: PARP inhibitors are the most frequent potential targeted therapy in HGSC. However, other targeted therapies remain relevant for investigation according to our mutational findings.
UR - http://www.scopus.com/inward/record.url?scp=85141794586&partnerID=8YFLogxK
U2 - 10.3390/ph15111324
DO - 10.3390/ph15111324
M3 - Journal article
C2 - 36355495
SN - 1424-8247
VL - 15
JO - Pharmaceuticals (Basel, Switzerland)
JF - Pharmaceuticals (Basel, Switzerland)
IS - 11
M1 - 1324
ER -