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An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer [RNA-Seq]

ABSTRACT: An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer [RNA-Seq]

PROVIDER: PRJNA1052125 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27203000_1.fastq.gz	Fastqsanger.gz
	SRR27203000_2.fastq.gz	Fastqsanger.gz
	SRR27203001_1.fastq.gz	Fastqsanger.gz
	SRR27203001_2.fastq.gz	Fastqsanger.gz
	SRR27203002_1.fastq.gz	Fastqsanger.gz

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An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer

Project description:An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer

| PRJNA1052123 | ENA

An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer [RNA-Seq]

Project description:Individual cancers are composed of heterogeneous tumor cells with distinct phenotypes and genotypes, with triple negative breast cancers (TNBC) demonstrating the most heterogeneity among breast cancer types. Variability in transcriptional phenotypes could meaningfully limit the efficacy of monotherapies and fuel drug resistance, although to an unknown extent. To determine if transcriptional differences between tumor cells lead to differential drug responses we performed single cell RNA-seq on cell line and PDX models of breast cancer revealing cell subpopulations in states associated with resistance to standard-of-care therapies. We found that TNBC models contained a subpopulation in an inflamed cellular state, often also present in human breast cancer samples. Inflamed cells display evidence of heightened cGAS/STING signaling which we demonstrate is sufficient to cause tumor cell resistance to chemotherapy. Accordingly, inflamed cells were enriched in human tumors taken after neoadjuvant chemotherapy and associated with early recurrence, highlighting the potential for diverse tumor cell states to promote drug resistance.

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An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer [scRNA-Seq]

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An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer [scRNA-Seq]

Project description:An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer [scRNA-Seq]

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Project description:Triple negative breast cancer is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study was to explore the clinical relevance of Lehmann triple negative breast cancer subtypes by identifying any differences in response to neoadjuvant chemotherapy among them.

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Response to Neoadjuvant Chemotherapy in Triple Negative Breast tumors.

Project description:In a cohort study of 7 women with primary invasive breast cancer, we obtained a tumor specimen before (biopsy) and after (tumorectomy) 4 cycles of NAC with epirubicine and cyclophosphamide, followed by 4 cycles of taxanes. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Affymetrix HuGene1.1ST. Molecular functions changing during chemotherapy were searched. Whole genome expression of triple negative breast cancer tissues were measured before and after four cycles neoadjuvant chemotherapy

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An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer.

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Project description:In the study presented here, a consecutively operated, well-defined cohort of 30 triple-negative breast cancer cases with neoadjuvant chemotherapy, followed up more than five years, was used to acquire TP53 signature composed of a total of 33 genes. Combining the response to NAC and the TP53signature score in triple-negative breast cancer was able to predict an unfavorable prognosis.

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