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76c1500b-471f-4d6b-a9fd-5e7416861048 - samples

ABSTRACT: Fastq files from RNAseq of breast cancer bone metastases PDX after treatment with IACS-010759. Five PDX are resistants to treatment and 6 are responders.

PROVIDER: EGAD00001009072 | EGA |

REPOSITORIES: EGA

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9bdd7700-1c57-429a-97ed-4a7ba99318f0 - samples

Project description:Fastq files from RNAseq of breast cancer bone metastases PDX of tumor HBC-124 treated by IACS-010759 (4 samples) or not (4 samples).

| EGAD00001009857 | EGA

Analyses of IACS-010759 treatment resistance on breast cancer bone metastases

Project description:Identification of biological mecanisms involved in resistance of breast cancer bone metastases to IACS treatment.

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Oxidative phosphorylation is a metabolic vulnerability of endocrine therapy and palbociclib resistant metastatic breast cancers

Project description:Resistance to endocrine treatments and CDK4/6 inhibitors is considered a near-inevitability in most patients with estrogen receptor positive breast cancers (ER + BC). By genomic and metabolomics analyses of patients' tumours, metastasis-derived patient-derived xenografts (PDX) and isogenic cell lines we demonstrate that a fraction of metastatic ER + BC is highly reliant on oxidative phosphorylation (OXPHOS). Treatment by the OXPHOS inhibitor IACS-010759 strongly inhibits tumour growth in multiple endocrine and palbociclib resistant PDX. Mutations in the PIK3CA/AKT1 genes are significantly associated with response to IACS-010759. At the metabolic level, in vivo response to IACS-010759 is associated with decreased levels of metabolites of the glutathione, glycogen and pentose phosphate pathways in treated tumours. In vitro, endocrine and palbociclib resistant cells show increased OXPHOS dependency and increased ROS levels upon IACS-010759 treatment. Finally, in ER + BC patients, high expression of OXPHOS associated genes predict poor prognosis. In conclusion, these results identify OXPHOS as a promising target for treatment resistant ER + BC patients.

2023-06-27 | MTBLS3342 | MetaboLights

IACS treatment on breast cancer bone metastases

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Expression data from Patient-derived tumor models (PDX) establish from bone metastases and match human breast primary tumor.

Project description:A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Bone is the most common metastatic site in ER+ patients, however bone metastases are technically challenging to biopsy and analyse. Difficulties concern both tumour tissue acquisition and techniques for analysis and RNA extractions. Patient-derived xenografts (PDX) of BC bone metastases have not been reported yet. For the first time we established PDX models from bone metastatic biopsies of patients progressing on ET and treated by vertebroplasty. PDX models were analysed at transcriptomic level and compared to patient’s early primary tumours to identify new therapeutic targets associated with endocrine resistance in the metastatic setting. Identification of activated signalling pathways in bone metastasis by comparative transcriptomic analyses of the bone metastasis derived PDX compared to the patients' primary breast tumor.

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Copy number data from Patient-Derived tumor models (PDX) establish from bone metastases of breast cancer.

Project description:A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Bone is the most common metastatic site in ER+ patients, however bone metastases are technically challenging to biopsy and analyse. Difficulties concern both tumour tissue acquisition and techniques for analysis and RNA extractions. Patient-derived xenografts (PDX) of BC bone metastases have not been reported yet. For the first time we established PDX models from bone metastatic biopsies of patients progressing on ET and treated by vertebroplasty. PDX models were analysed at genomic level to identify new therapeutic targets associated with endocrine resistance in the metastatic setting. Identification of chromosomic alterations in bone metastasis derived PDX.

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RNA sequencing data from triple-negative breast cancer patient-derived xenografts (PDX)

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Project description:Sequence of breast cancer bone metastases PDX obtained by 2 targeted panels

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23eaca14-0712-42a6-b37a-55b52ac942b3 - samples

Project description:Sequence of breast cancer bone metastases PDX obtained by 2 targeted panels

| EGAD00001010856 | EGA

17ea106f-cf0a-448c-a6d6-b2dd3ae4086e - samples

Project description:Targeted sequencing analyses was made on samples of PDX engrafted with breast cancer bone metastases, 2 PDX acquired resistance to palbociclib.

| EGAD00001006070 | EGA

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