Targeting PI3K, FGFR, CDK4/6 Signaling Pathways Together With Cytostatics and Radiotherapy in Two Medulloblastoma Cell Lines
ObjectivesMedulloblastoma (MB) is treated with surgery and chemotherapy, with or without irradiation, but unfortunately >20% of the patients are not cured, and treatment comes with serious long-term side effects, so novel treatments are urgently needed. Phosphoinositide 3-kinases (PI3K), fibr...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-09-01
|
Series: | Frontiers in Oncology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.748657/full |
id |
doaj-8a7914929737482287a7f7ecd227847a |
---|---|
record_format |
Article |
spelling |
doaj-8a7914929737482287a7f7ecd227847a2021-09-24T06:14:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.748657748657Targeting PI3K, FGFR, CDK4/6 Signaling Pathways Together With Cytostatics and Radiotherapy in Two Medulloblastoma Cell LinesMonika LukoseviciuteHenrietta MaierEleni Poulou-SidiropoulouErika RosendahlStefan HolzhauserTina DalianisOurania N. KostopoulouObjectivesMedulloblastoma (MB) is treated with surgery and chemotherapy, with or without irradiation, but unfortunately >20% of the patients are not cured, and treatment comes with serious long-term side effects, so novel treatments are urgently needed. Phosphoinositide 3-kinases (PI3K), fibroblast growth factor receptors (FGFR), and cyclin-D kinases (CDK) play critical roles in cancer, and especially PI3K is crucial in MB, so here targeted therapies against them were explored.MethodsMB cell lines DAOY and UW228-3 were exposed to PI3K (BYL719), FGFR (JNJ-42756493), and CDK4/6 (PD-0332991) inhibitors, as single or combined treatments, and their viability, cell confluence, apoptosis, and cytotoxicity were examined. Moreover, the inhibitors were combined with cisplatin, vincristine, or irradiation.ResultsSingle treatments with FGFR, PI3K, or CDK4/6 inhibitors decreased viability and proliferation slightly; however, when combining two inhibitors, or the inhibitors with irradiation, sensitivity was enhanced and lower doses could be used. A more complex pattern was obtained when combining the inhibitors with cisplatin and vincristine.ConclusionsThe data suggest that combination treatments with PI3K, FGFR, and CDK4/6 inhibitors for MB could be beneficial and their use should be pursued further. Likewise, their combination with irradiation gave positive effects, while the addition of cisplatin and vincristine resulted in more complex patterns, which need to be investigated further.https://www.frontiersin.org/articles/10.3389/fonc.2021.748657/fullchildhood cancermedulloblastoma (MB)targeted therapyPI3K inhibitorsFGFR inhibitorsCDK4/6 inhibitors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Monika Lukoseviciute Henrietta Maier Eleni Poulou-Sidiropoulou Erika Rosendahl Stefan Holzhauser Tina Dalianis Ourania N. Kostopoulou |
spellingShingle |
Monika Lukoseviciute Henrietta Maier Eleni Poulou-Sidiropoulou Erika Rosendahl Stefan Holzhauser Tina Dalianis Ourania N. Kostopoulou Targeting PI3K, FGFR, CDK4/6 Signaling Pathways Together With Cytostatics and Radiotherapy in Two Medulloblastoma Cell Lines Frontiers in Oncology childhood cancer medulloblastoma (MB) targeted therapy PI3K inhibitors FGFR inhibitors CDK4/6 inhibitors |
author_facet |
Monika Lukoseviciute Henrietta Maier Eleni Poulou-Sidiropoulou Erika Rosendahl Stefan Holzhauser Tina Dalianis Ourania N. Kostopoulou |
author_sort |
Monika Lukoseviciute |
title |
Targeting PI3K, FGFR, CDK4/6 Signaling Pathways Together With Cytostatics and Radiotherapy in Two Medulloblastoma Cell Lines |
title_short |
Targeting PI3K, FGFR, CDK4/6 Signaling Pathways Together With Cytostatics and Radiotherapy in Two Medulloblastoma Cell Lines |
title_full |
Targeting PI3K, FGFR, CDK4/6 Signaling Pathways Together With Cytostatics and Radiotherapy in Two Medulloblastoma Cell Lines |
title_fullStr |
Targeting PI3K, FGFR, CDK4/6 Signaling Pathways Together With Cytostatics and Radiotherapy in Two Medulloblastoma Cell Lines |
title_full_unstemmed |
Targeting PI3K, FGFR, CDK4/6 Signaling Pathways Together With Cytostatics and Radiotherapy in Two Medulloblastoma Cell Lines |
title_sort |
targeting pi3k, fgfr, cdk4/6 signaling pathways together with cytostatics and radiotherapy in two medulloblastoma cell lines |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-09-01 |
description |
ObjectivesMedulloblastoma (MB) is treated with surgery and chemotherapy, with or without irradiation, but unfortunately >20% of the patients are not cured, and treatment comes with serious long-term side effects, so novel treatments are urgently needed. Phosphoinositide 3-kinases (PI3K), fibroblast growth factor receptors (FGFR), and cyclin-D kinases (CDK) play critical roles in cancer, and especially PI3K is crucial in MB, so here targeted therapies against them were explored.MethodsMB cell lines DAOY and UW228-3 were exposed to PI3K (BYL719), FGFR (JNJ-42756493), and CDK4/6 (PD-0332991) inhibitors, as single or combined treatments, and their viability, cell confluence, apoptosis, and cytotoxicity were examined. Moreover, the inhibitors were combined with cisplatin, vincristine, or irradiation.ResultsSingle treatments with FGFR, PI3K, or CDK4/6 inhibitors decreased viability and proliferation slightly; however, when combining two inhibitors, or the inhibitors with irradiation, sensitivity was enhanced and lower doses could be used. A more complex pattern was obtained when combining the inhibitors with cisplatin and vincristine.ConclusionsThe data suggest that combination treatments with PI3K, FGFR, and CDK4/6 inhibitors for MB could be beneficial and their use should be pursued further. Likewise, their combination with irradiation gave positive effects, while the addition of cisplatin and vincristine resulted in more complex patterns, which need to be investigated further. |
topic |
childhood cancer medulloblastoma (MB) targeted therapy PI3K inhibitors FGFR inhibitors CDK4/6 inhibitors |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.748657/full |
work_keys_str_mv |
AT monikalukoseviciute targetingpi3kfgfrcdk46signalingpathwaystogetherwithcytostaticsandradiotherapyintwomedulloblastomacelllines AT henriettamaier targetingpi3kfgfrcdk46signalingpathwaystogetherwithcytostaticsandradiotherapyintwomedulloblastomacelllines AT elenipoulousidiropoulou targetingpi3kfgfrcdk46signalingpathwaystogetherwithcytostaticsandradiotherapyintwomedulloblastomacelllines AT erikarosendahl targetingpi3kfgfrcdk46signalingpathwaystogetherwithcytostaticsandradiotherapyintwomedulloblastomacelllines AT stefanholzhauser targetingpi3kfgfrcdk46signalingpathwaystogetherwithcytostaticsandradiotherapyintwomedulloblastomacelllines AT tinadalianis targetingpi3kfgfrcdk46signalingpathwaystogetherwithcytostaticsandradiotherapyintwomedulloblastomacelllines AT ouraniankostopoulou targetingpi3kfgfrcdk46signalingpathwaystogetherwithcytostaticsandradiotherapyintwomedulloblastomacelllines |
_version_ |
1717370119465730048 |