Effects of the multikinase inhibitors Sorafenib and Regorafenib in PTEN deficient neoplasias.
The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) axis is frequently dysregulated in cancer due to mutations in different nodes of the pathway or constitutive activation of receptor tyrosine kinases. Multikinase inhibitors as sorafenib and regorafenib represent a therapeutic approach for the treatment of these types of tumours. In the present study, we have evaluated the anti-tumoural effects of Sorafenib and Regorafenib on endometrial, prostate and thyroid neoplasias. Both inhibitors reduced cell viability in vitro and lead to a disruption of the PI3K/AKT/mTOR pathway. In vivo, we have demonstrated that Sorafenib and Regorafenib reduce thyroid hyperplasias induced by the loss of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), although none of the treatments eliminated the disease. Altogether, we present the first study that correlates the response to multikinase inhibitors with a specific mutation. Moreover, this is the first report characterising the response to Regorafenib in thyroid, prostate and endometrial neoplasias.
Oncologic Pathology Group, Dept. Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, IRBLleida, Lleida, Spain.
Cristina
C
Mirantes
Oncologic Pathology Group, Dept. Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, IRBLleida, Lleida, Spain.
Maria Alba
MA
Dosil
Oncologic Pathology Group, Dept. Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, IRBLleida, Lleida, Spain.
Núria
N
Eritja
Oncologic Pathology Group, Dept. Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, IRBLleida, Lleida, Spain.
Isidre
I
Felip
Oncologic Pathology Group, Dept. Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, IRBLleida, Lleida, Spain.
Sònia
S
Gatius
Oncologic Pathology Group, Dept. Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, IRBLleida, Lleida, Spain.
Maria
M
Santacana
Oncologic Pathology Group, Dept. Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, IRBLleida, Lleida, Spain.
Xavier
X
Matias-Guiu
Oncologic Pathology Group, Dept. Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, IRBLleida, Lleida, Spain. Electronic address: dolcet@cmb.udl.cat.
Xavier
X
Dolcet
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor / Q000187:drug effects; D004195:Disease Models, Animal; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051059:PTEN Phosphohydrolase / Q000172:deficiency; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C559147:regorafenib; D009536:Niacinamide; D000077157:Sorafenib; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Carcinoma; Multikinase inhibitor; PTEN; Regorafenib; Sorafenib