Disentangling ERBB Signaling in Breast Cancer Subtypes-A Model-Based Analysis.

Targeted therapies have shown striking success in the treatment of cancer over the last years. However, their specific effects on an individual tumor appear to be varying and difficult to predict. Using an integrative modeling approach that combines mechanistic and regression modeling, we gained insights into the response mechanisms of breast cancer cells due to different ligand-drug combinations.

Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts.

HER3 is highly expressed in luminal breast cancer subtypes. Its activation by NRG1 promotes activation of AKT and ERK1/2, contributing to tumour progression and therapy resistance. HER3-targeting agents that block this activation, are currently under phase 1/2 clinical studies, and although they have shown favorable tolerability, their activity as a single agent has proven to be limited.

IFNβ1 secreted by breast cancer cells undergoing chemotherapy reprograms stromal fibroblasts to support tumour growth after treatment.

Chemotherapy (CTX) remains the standard of care for most aggressive tumours, including breast cancer (BC). In BC chemotherapeutic regimens, the maximum tolerated dose of cytotoxic drugs is administered at regular intervals, and cancer cells can re-grow or adapt during the resting periods between cycles. The impact of the tumour microenvironment on the fate of cancer cells after CTX remains poorly understood.

Noncanonical TGFβ Pathway Relieves the Blockade of IL1β/TGFβ-Mediated Crosstalk between Tumor and Stroma: TGFBR1 and TAK1 Inhibition in Colorectal Cancer.

Purpose: The aim of the study is blocking the recruitment of a protective stroma by altering the crosstalk between normal stromal cells and tumor cells for stripping tumors of the protection conferred by the microenvironment.

Experimental Design: A transcriptomic analysis of cocultured normal colonic fibroblasts and colorectal tumor cells was performed. We focused on the study of molecules that mediate the communication between both compartments and that entail fibroblasts' activation and the alteration of the sensitivity to chemotherapy.

Carcinoma-associated fibroblasts affect sensitivity to oxaliplatin and 5FU in colorectal cancer cells.

The importance of tumor microenvironment (TME) as a relevant contributor to cancer progression and its role in the development of de novo resistance to targeted therapies has become increasingly apparent. However, the mechanisms of microenvironment-mediated drug resistance for nonspecific conventional chemotherapeutic agents, such as platinum compounds or antimetabolites, are still unclear.Here we describe a mechanism induced by soluble factors released by carcinoma-associated fibroblasts (CAFs) that induce the translocation of AKT, Survivin and P38 to the nucleus of tumor cells.

A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer.

Based on 108 differentially expressed genes between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts we recently reported, a 5-gene classifier for relapse prediction in Stage II/III colorectal cancer (CRC ) was developed. Its predictive value was validated in datasets GSE17538, GSE33113 and GSE14095. An additional validation was performed in a metacohort (n=317) and 142 CRC patients by means of RT-PCR.

Differences between CAFs and their paired NCF from adjacent colonic mucosa reveal functional heterogeneity of CAFs, providing prognostic information.

Little is known about the difference in gene expression between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts (NCFs) in colorectal cancer. Paired CAFs and NCFs were isolated from eight primary human colorectal carcinoma specimens. In culture conditions, soluble factors secreted by CAFs in the conditioned media increased clonogenicity and migration of epithelial cancer cells lines to a greater extent than did NCF.

A monotonic and prognostic genomic signature from fibroblasts for colorectal cancer initiation, progression, and metastasis.

Unlabelled: The differential gene expression patterns between normal colonic fibroblasts (NCF), carcinoma-associated fibroblasts from primary tumors (CAF-PT), and CAFs from hepatic metastasis (CAF-LM) are hypothesized to be useful for predicting relapse in primary tumors. A transcriptomic profile of NCF (n = 9), CAF-PT (n = 14), and CAF-LM (n = 11) was derived. Prediction Analysis of Microarrays (PAM) was used to obtain molecular details for each fibroblast class, and differentially expressed transcripts were used to classify patients according to recurrence status.

Lurbinectedin (PM01183), a new DNA minor groove binder, inhibits growth of orthotopic primary graft of cisplatin-resistant epithelial ovarian cancer.

Purpose: Epithelial ovarian cancer (EOC) is the fifth leading cause of death in women diagnosed with gynecologic malignancies. The low survival rate is because of its advanced-stage diagnosis and either intrinsic or acquired resistance to standard platinum-based chemotherapy. So, the development of effective innovative therapeutic strategies to overcome cisplatin resistance remains a high priority.

Hepatic carcinoma-associated fibroblasts promote an adaptative response in colorectal cancer cells that inhibit proliferation and apoptosis: nonresistant cells die by nonapoptotic cell death.

Carcinoma-associated fibroblasts (CAFs) are important contributors of microenvironment in determining the tumor's fate. This study aimed to compare the influence of liver microenvironment and primary tumor microenvironment on the behavior of colorectal carcinoma. Conditioned medium (CM) from normal colonic fibroblasts (NCFs), CAFs from primary tumor (CAF-PT) or liver metastasis (CAF-LM) were obtained.