Combination of iron deprivation and chemotherapies treatments in breast cancer xenografts
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ABSTRACT:
PROVIDER: PRJNA417459 | ENA |
REPOSITORIES: ENA
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Project description:To ensure their high proliferation rate, tumor cells display an iron metabolic disorder with increased iron needs, making them more susceptible to iron deprivation. This vulnerability could be a therapeutic target. In breast cancers, the development of new therapeutic approaches is urgently needed for patients with triple negative tumors which frequently relapse after chemotherapy and suffer from a lack of targeted therapies. Anticancer activity of iron chelator deferasirox (DFX) assessed in monotherapy do not appear to be effective enough to treat breast cancer progression. In this work, we demonstrated that DFX synergizes with standard chemotherapeutic agents such as with doxorubicin, cisplatin and carboplatin to inhibit cell proliferation and induce apoptosis and autophagy in TNBC cell lines. Moreover, the combination of DFX with doxorubicin and cyclophosphamide allowed to delay or avoid recurrences in breast cancer patient-derived xenografts without increasing the side-effects of chemotherapies alone or altering global iron storage of mice. Antitumor synergy of DFX and doxorubicin involves down-regulation of PI3K and NF-κB pathways. Furthermore, as TNBC patients with low iron tumor dynamic in their tumor present a good prognosis, we thought that iron deprivation mediated by iron chelators may all the more increase the effectiveness of conventional chemotherapies for TNBC treatments.
2020-11-06 | GSE106618 | GEO
Project description:Androgen deprivation is a standard of care front-line therapy for human prostate cancer, however, majority of patients will eventally develop resistance to androgen deprivation. In this study, using a human prostate cancer xenograft model -LuCaP35, we examiend the gene expression changes after castration. We compare the gene expression of 5 LuCaP35 xenografts from non-treated mice (Control), and 5 androgen-deprived LuCaP35 xenografts from castrated mice (Castration).
2011-12-06 | E-GEOD-33316 | biostudies-arrayexpress
Project description:Acute promyelocytic leukaemia (APL) can be cured by the co-administration of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA). These small molecules relieve the differentiation blockade of the cancerous promyelocytes and trigger their maturation into functional neutrophils, which are physiologically primed for apoptosis. This normalization therapy uses low dose treatments and represents a compelling alternative to cytotoxic anticancer chemotherapy. However, the serendipitous discovery of this combination treatment prevented the establishment of methodologies to screen for novel combination treatments consisting of inducers of differentiation and other metallopharmaceuticals. Here, we present an experimental framework that enables interrogating the suitability, directionality and extent of normalization of novel combination treatments. Since the endpoint of this anticancer treatment is remodelling of cancer phenotypes, this approach requires a mechanism-driven understanding of the drug-induced cellular adaptions along the path to mature neutrophils. For this purpose, label-free quantification proteomics is used to probe the proteome changes upon differentiation and metal(-loid) treatment on the molecular level in a panel of ATRA-responsive and ATRA-non-responsive acute myeloid leukaemia (AML) cell lines, including APL. The induction of differentiation was confirmed by the up-regulation of canonical surface markers (e.g. CD11β) and validated by flow cytometry. The regulation of key transcription factors in this panel of AML cell lines reflects their position in the myeloid differentiation cascade (e.g. SPI1, GFI-1 and CEBPE). The additive/synergistic contributions of ATO to the combination treatment were thoroughly characterized and include changes in metabolic activities, as well as protein signatures related to management of reactive oxygen species and an integrated stress response. The latter two are also characteristic for the organoruthenium-based drug candidate plecstatin-1, which was recently shown to modulate the scaffold protein plectin. The combination of differentiation-induction and plecstatin-1 treatment featured a striking similarity in the responsiveness of the AML cancer cells compared to ATO+ATRA. It turned out to be at least equivalent in the regulation of key processes underlying normalization therapy in AML with granulocytic maturation. By exploiting response patterns of AML cancer cells induced by the ATO+ATRA combination treatment, this approach may allow identifying novel small molecule combinations, which may have the potential to achieve normalization and thus therapeutic benefit beyond APL.
2022-02-22 | PXD019619 | Pride
Project description:The purpose of this study was to characterise the effects of trastuzumab and pertuzumab, either as single agents or as combination therapy on gene and protein expression in human ovarian cancer in vivo. Illumina BeadChips were used to profile the transcriptome after four days treatment of SKOV3 tumor xenografts. Although genes involved with HER2, MAP-kinase and p53 signaling pathways were commonly induced by all treatments, a greater number and variety of genes were differentially expressed by the complementary combination therapies compared to either drug on its own. The protein level of the CDK-inhibitors p21 and p27 were increased in response to both agents alone and further by the combination; pERK signaling was inhibited by all treatments; but only pertuzumab alone inhibited pAkt signaling. The expression of proliferation, apoptosis, cell division and cell cycle markers was distinct in a panel of primary ovarian cancer xenografts, suggesting heterogeneity of response in ovarian cancer and the need to establish biomarkers of response. This first comprehensive study of the molecular response to trastuzumab, pertuzumab and combination therapy in vivo highlights that there are both common and distinct downstream effects to different HER2 antibodies and that pathways may be invoked more strongly or in a different manner by a combination of agents. Some of the in vivo results for ovarian tumors differ from previous in vitro studies in breast cancer cells, emphasizing that the molecular response to anti-cancer agents involves variable and complex disease-specific interactions of signaling mechanisms. SCOV3 Ovarian cell line xenografts treated with Trastuzumab, pertuzumab or combination after 4 days
2012-05-02 | E-GEOD-31432 | biostudies-arrayexpress
Project description:The Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D). PBS vs each drug combination
2013-03-06 | E-GEOD-44857 | biostudies-arrayexpress
Project description:RPPA profiling of ES8 Ewing sarcoma xenografts after Endoglin-targeting antibody-drug conjugate treatments
| PRJNA472943 | ENA
Project description:Primary breast cancer xenografts Two primary xenografts with different treatments
2013-02-24 | E-GEOD-36075 | biostudies-arrayexpress
Project description:Androgen Deprivation Therapy Potentiates the Efficacy of Vascular Targeted Photodynamic Therapy of Prostate Cancer Xenografts
| PRJNA431647 | ENA
Project description:The Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D).
2013-03-06 | GSE44857 | GEO
Project description:Murine C26 tumor xenografts displayed different responses to the treatments of PBS, Doxorubicin (Dox), and chimeric polypeptide (CP)-Dox conjugates. We used microarrays to globally study gene expression underlying these different responses and identified distinct classes of up-regulated or down-regulated genes upon treatment. C26 murine colon carcinoma xenografts were analyzed at 48 hours after treatment with CP-Dox, free Dox, and PBS (control). This study involved four replicates of each treatment.
2010-07-15 | E-GEOD-17115 | biostudies-arrayexpress