Seviteronel plus chemotherapy is a new targeted combination therapy to treat triple-negative breast cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA764708 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15972632_1.fastq.gz | Fastqsanger.gz | |||
| SRR15972632_2.fastq.gz | Fastqsanger.gz | |||
| SRR15972633_1.fastq.gz | Fastqsanger.gz | |||
| SRR15972633_2.fastq.gz | Fastqsanger.gz | |||
| SRR15972634_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:cmLumiOpto gene therapy in combination with chemotherapy to treat triple negative breast cancer.
| PRJNA1308851 | ENA
Project description:Therapeutic strategies that improve survival outcomes for advanced-stage breast cancers have proven a major clinical challenge. Here, we define an androgen receptor signalling network that governs the maintenance and de novo formation of cancer stem cells in triple-negative breast cancer. In response to chemotherapy, androgen receptor activation switches cells into a cancer stem cell state, while androgen receptor antagonism suppresses cancer stem cell formation and function. In vivo, we validate that the androgen receptor antagonist, seviteronel, significantly improves chemotherapy-mediated inhibition of primary and metastatic tumour growth.
2023-12-03 | GSE184455 | GEO
Project description:Triple-negative breast cancer (TNBC) is aggressive, resistant to chemotherapy, and prone to recurrence. While PARP inhibitors (PARPi) help some patients, most do not respond. We developed a novel therapy combining mitochondria-targeted luminoptogenetics (cmLumiOpto) with PARPi to enhance treatment. Delivered via an anti-CD276 monoclonal antibody-conjugated exosome-AAV (mAb-Exo-AAV), cmLumiOpto disrupts mitochondrial membrane potential, inducing cancer cell death. In vitro, the combination increased cytotoxicity; in vivo, it reduced tumor burden by 95–100%, suppressed xenograft growth, and blocked metastasis in TNBC models. Mechanistic studies showed mitochondrial depolarization, DNA damage, cytokine release, and immune infiltration, highlighting a promising strategy for TNBC therapy. The mechanism of action was further explained through bulk RNA sequencing post-treatment. These findings highlight the therapeutic potential of our cmLumiOpto gene therapy for treatment of triple negative breast cancers.
2026-01-12 | GSE305990 | GEO
Project description:Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC), which exhibited a poor prognosis due to the highly tumor microenvironmental heterogeneity and specific mutations. Recent studies have investigated the different celltypes in TNBC microenvironment, however, the effects of immunotherapy and chemotherapy combination therapy on TNBC are largely unknown. Here we explored the changes of TNBC microenvironment upon immunotherapy and chemotherapy combination therapy by scRNA-seq. We found that the insensitive (PCPAi) patient exhibited high CNV score in tumor cells, lower cytotoxicity in CD8+ T cells, higher quiescence and exhaustion characteristics CD4+ T cells, compared to sensitive (PCPAs) patient. Meanwhile, the PCPAi patient showed more complex fibroblasts and tumor-associated macrophages heterogeneity. We also found the key ligand-receptor based cellular interactions, such as SPP1 and TGFβ. These results provide a research basis for us to understand the microenvironment changes and therapeutic efficacy of triple negative breast cancer after chemotherapy combined with immunotherapy.
2025-12-31 | GSE302453 | GEO
Project description:Immune checkpoint inhibitors combined with chemotherapy represent a promising treatment option in triple-negative breast cancer (TNBC). However, response rates are still relatively low necessitating the design of novel therapeutic strategies to improve clinical outcomes. Here, we describe a triple combination of anti-PDL-1 immune checkpoint blockade, epigenetic modulation thorough BET bromodomain inhibition, and chemotherapy with paclitaxel that effectively inhibits both primary and metastatic tumor growth in two different syngeneic murine breast cancer models. Detailed cellular and molecular profiling of tumors from single and combination treatment arms revealed increased T and B cell infiltration and macrophage reprogramming from M1 to a M2 phenotype in mice treated with triple combination.
2023-08-15 | GSE229422 | GEO
Project description:Immune checkpoint inhibitors combined with chemotherapy represent a promising treatment option in triple-negative breast cancer (TNBC). However, response rates are still relatively low necessitating the design of novel therapeutic strategies to improve clinical outcomes. Here, we describe a triple combination of anti-PDL-1 immune checkpoint blockade, epigenetic modulation thorough BET bromodomain inhibition, and chemotherapy with paclitaxel that effectively inhibits both primary and metastatic tumor growth in two different syngeneic murine breast cancer models. Detailed cellular and molecular profiling of tumors from single and combination treatment arms revealed increased T and B cell infiltration and macrophage reprogramming from M1 to a M2 phenotype in mice treated with triple combination.
2023-08-15 | GSE229426 | GEO
Project description:Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive disease where limited therapeutic options are available. A significant correlation exists between presence of intratumoral macrophages, tumor progression, and poor outcomes in TNBC. Preclinical in vivo studies revealed that inhibition of myelomonocytic colony stimulating factor 1 (CSF1) or its receptor (CSF1R), plus cytotoxic therapy decreases primary tumor growth kinetics and pulmonary metastases by CD8+ T cell-dependent mechanisms. To evaluate safety and tolerability of this immune-based therapeutic strategy, we conducted a phase Ib/II clinical trial evaluating Pexidartinib (PLX3397), a small molecule CSF1R inhibitor plus Eribulin chemotherapy in patients with heavily pretreated metastatic TNBC. Correlate analyses from baseline revealed increased leukocyte activation biomarkers, increased presence of CD8+ and CD4+ T central memory cells, and increased PD-1 expression on CD4+ T cells in patients experiencing a partial response or stable disease, together providing evidence of enhanced anti-tumor immunity. We hypothesized that addition of either PD-1 and PD-L1-blockade following CSF1R inhibition and chemotherapy would lead to a further enhanced anti-tumor T cell response. To test this, we evaluated tumor-bearing MMTV-PyMT transgenic mice comparing addition of PD-1- or PD-L1-blockade to Pexidartinib/Paclitaxel therapy. This revealed tumor regression in ~60% of transgenic mice with combined PD-1, but not PD-L1-blockade. Analysis of mammary tumors from mice treated with the PD-1 combination revealed activation and expansion of short-lived effector and memory T cells, and unique clonally-expanded T cells not observed with the PD-L1-blockade combination. These clinical and preclinical findings together provide rationale for addition of CSF1/CSF1R inhibitors to chemotherapy and PD-1-blocakde to further improve outcomes for patients with BC.
2026-02-23 | GSE267165 | GEO
Project description:Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive disease where limited therapeutic options are available. A significant correlation exists between presence of intratumoral macrophages, tumor progression, and poor outcomes in TNBC. Preclinical in vivo studies revealed that inhibition of myelomonocytic colony stimulating factor 1 (CSF1) or its receptor (CSF1R), plus cytotoxic therapy decreases primary tumor growth kinetics and pulmonary metastases by CD8+ T cell-dependent mechanisms. To evaluate safety and tolerability of this immune-based therapeutic strategy, we conducted a phase Ib/II clinical trial evaluating Pexidartinib (PLX3397), a small molecule CSF1R inhibitor plus Eribulin chemotherapy in patients with heavily pretreated metastatic TNBC. Correlate analyses from baseline revealed increased leukocyte activation biomarkers, increased presence of CD8+ and CD4+ T central memory cells, and increased PD-1 expression on CD4+ T cells in patients experiencing a partial response or stable disease, together providing evidence of enhanced anti-tumor immunity. We hypothesized that addition of either PD-1 and PD-L1-blockade following CSF1R inhibition and chemotherapy would lead to a further enhanced anti-tumor T cell response. To test this, we evaluated tumor-bearing MMTV-PyMT transgenic mice comparing addition of PD-1- or PD-L1-blockade to Pexidartinib/Paclitaxel therapy. This revealed tumor regression in ~60% of transgenic mice with combined PD-1, but not PD-L1-blockade. Analysis of mammary tumors from mice treated with the PD-1 combination revealed activation and expansion of short-lived effector and memory T cells, and unique clonally-expanded T cells not observed with the PD-L1-blockade combination. These clinical and preclinical findings together provide rationale for addition of CSF1/CSF1R inhibitors to chemotherapy and PD-1-blocakde to further improve outcomes for patients with BC.
2026-02-23 | GSE267168 | GEO
Project description:Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive disease where limited therapeutic options are available. A significant correlation exists between presence of intratumoral macrophages, tumor progression, and poor outcomes in TNBC. Preclinical in vivo studies revealed that inhibition of myelomonocytic colony stimulating factor 1 (CSF1) or its receptor (CSF1R), plus cytotoxic therapy decreases primary tumor growth kinetics and pulmonary metastases by CD8+ T cell-dependent mechanisms. To evaluate safety and tolerability of this immune-based therapeutic strategy, we conducted a phase Ib/II clinical trial evaluating Pexidartinib (PLX3397), a small molecule CSF1R inhibitor plus Eribulin chemotherapy in patients with heavily pretreated metastatic TNBC. Correlate analyses from baseline revealed increased leukocyte activation biomarkers, increased presence of CD8+ and CD4+ T central memory cells, and increased PD-1 expression on CD4+ T cells in patients experiencing a partial response or stable disease, together providing evidence of enhanced anti-tumor immunity. We hypothesized that addition of either PD-1 and PD-L1-blockade following CSF1R inhibition and chemotherapy would lead to a further enhanced anti-tumor T cell response. To test this, we evaluated tumor-bearing MMTV-PyMT transgenic mice comparing addition of PD-1- or PD-L1-blockade to Pexidartinib/Paclitaxel therapy. This revealed tumor regression in ~60% of transgenic mice with combined PD-1, but not PD-L1-blockade. Analysis of mammary tumors from mice treated with the PD-1 combination revealed activation and expansion of short-lived effector and memory T cells, and unique clonally-expanded T cells not observed with the PD-L1-blockade combination. These clinical and preclinical findings together provide rationale for addition of CSF1/CSF1R inhibitors to chemotherapy and PD-1-blocakde to further improve outcomes for patients with BC.
2026-02-23 | GSE267167 | GEO
Project description:Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive disease where limited therapeutic options are available. A significant correlation exists between presence of intratumoral macrophages, tumor progression, and poor outcomes in TNBC. Preclinical in vivo studies revealed that inhibition of myelomonocytic colony stimulating factor 1 (CSF1) or its receptor (CSF1R), plus cytotoxic therapy decreases primary tumor growth kinetics and pulmonary metastases by CD8+ T cell-dependent mechanisms. To evaluate safety and tolerability of this immune-based therapeutic strategy, we conducted a phase Ib/II clinical trial evaluating Pexidartinib (PLX3397), a small molecule CSF1R inhibitor plus Eribulin chemotherapy in patients with heavily pretreated metastatic TNBC. Correlate analyses from baseline revealed increased leukocyte activation biomarkers, increased presence of CD8+ and CD4+ T central memory cells, and increased PD-1 expression on CD4+ T cells in patients experiencing a partial response or stable disease, together providing evidence of enhanced anti-tumor immunity. We hypothesized that addition of either PD-1 and PD-L1-blockade following CSF1R inhibition and chemotherapy would lead to a further enhanced anti-tumor T cell response. To test this, we evaluated tumor-bearing MMTV-PyMT transgenic mice comparing addition of PD-1- or PD-L1-blockade to Pexidartinib/Paclitaxel therapy. This revealed tumor regression in ~60% of transgenic mice with combined PD-1, but not PD-L1-blockade. Analysis of mammary tumors from mice treated with the PD-1 combination revealed activation and expansion of short-lived effector and memory T cells, and unique clonally-expanded T cells not observed with the PD-L1-blockade combination. These clinical and preclinical findings together provide rationale for addition of CSF1/CSF1R inhibitors to chemotherapy and PD-1-blocakde to further improve outcomes for patients with BC.
2026-02-23 | GSE267164 | GEO