Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones.
Development of resistance to endocrine therapy is a clinical issue in estrogen receptor (ER)-positive breast cancer. Here we show that persistent activation of AKT/mTOR signaling is crucial to the acquisition of letrozole resistance in cell clones generated from MCF-7/AROM-1 aromatase-expressing bre...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2012
|
| _version_ | 1826278729901408256 |
|---|---|
| author | Cavazzoni, A Bonelli, M Fumarola, C La Monica, S Airoud, K Bertoni, R Alfieri, R Galetti, M Tramonti, S Galvani, E Harris, A Martin, L Andreis, D Bottini, A Generali, D Petronini, P |
| author_facet | Cavazzoni, A Bonelli, M Fumarola, C La Monica, S Airoud, K Bertoni, R Alfieri, R Galetti, M Tramonti, S Galvani, E Harris, A Martin, L Andreis, D Bottini, A Generali, D Petronini, P |
| author_sort | Cavazzoni, A |
| collection | OXFORD |
| description | Development of resistance to endocrine therapy is a clinical issue in estrogen receptor (ER)-positive breast cancer. Here we show that persistent activation of AKT/mTOR signaling is crucial to the acquisition of letrozole resistance in cell clones generated from MCF-7/AROM-1 aromatase-expressing breast cancer cells after prolonged letrozole exposure. ERα plays a marginal role in this context. As a proof of concept, the association between PI3K/AKT/mTOR signaling and insensitivity to endocrine therapies was confirmed in breast cancer patients who developed early letrozole resistance in neoadjuvant setting. In addition our results suggest that, regardless of the mechanism mediating the activation of AKT/mTOR pathway, either RAD001 or NVP-BEZ235 treatment may represent a promising strategy to overcome acquired resistance to letrozole in breast cancers dependent on AKT/mTOR signaling. |
| first_indexed | 2024-03-06T23:48:19Z |
| format | Journal article |
| id | oxford-uuid:71bb51d9-61d4-4ada-8422-8882fbf6780b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:48:19Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:71bb51d9-61d4-4ada-8422-8882fbf6780b2022-03-26T19:45:32ZOvercoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:71bb51d9-61d4-4ada-8422-8882fbf6780bEnglishSymplectic Elements at Oxford2012Cavazzoni, ABonelli, MFumarola, CLa Monica, SAiroud, KBertoni, RAlfieri, RGaletti, MTramonti, SGalvani, EHarris, AMartin, LAndreis, DBottini, AGenerali, DPetronini, PDevelopment of resistance to endocrine therapy is a clinical issue in estrogen receptor (ER)-positive breast cancer. Here we show that persistent activation of AKT/mTOR signaling is crucial to the acquisition of letrozole resistance in cell clones generated from MCF-7/AROM-1 aromatase-expressing breast cancer cells after prolonged letrozole exposure. ERα plays a marginal role in this context. As a proof of concept, the association between PI3K/AKT/mTOR signaling and insensitivity to endocrine therapies was confirmed in breast cancer patients who developed early letrozole resistance in neoadjuvant setting. In addition our results suggest that, regardless of the mechanism mediating the activation of AKT/mTOR pathway, either RAD001 or NVP-BEZ235 treatment may represent a promising strategy to overcome acquired resistance to letrozole in breast cancers dependent on AKT/mTOR signaling. |
| spellingShingle | Cavazzoni, A Bonelli, M Fumarola, C La Monica, S Airoud, K Bertoni, R Alfieri, R Galetti, M Tramonti, S Galvani, E Harris, A Martin, L Andreis, D Bottini, A Generali, D Petronini, P Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. |
| title | Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. |
| title_full | Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. |
| title_fullStr | Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. |
| title_full_unstemmed | Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. |
| title_short | Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. |
| title_sort | overcoming acquired resistance to letrozole by targeting the pi3k akt mtor pathway in breast cancer cell clones |
| work_keys_str_mv | AT cavazzonia overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT bonellim overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT fumarolac overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT lamonicas overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT airoudk overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT bertonir overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT alfierir overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT galettim overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT tramontis overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT galvanie overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT harrisa overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT martinl overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT andreisd overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT bottinia overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT generalid overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones AT petroninip overcomingacquiredresistancetoletrozolebytargetingthepi3kaktmtorpathwayinbreastcancercellclones |