Publications by authors named "Mercedes Marin-Aguilera"
Unlabelled: Alterations in the tumor suppressor genes (TSGs) , , and are associated with treatment resistance, worse survival, and aggressive variants of prostate cancer (AVPC). We previously developed and validated a signature reflecting low TSG expression (TSG) that was associated with poor outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) ± docetaxel. The aim of this multicenter retrospective study was to validate the TSG signature in patients with mHSPC treated with ADT and an androgen receptor pathway inhibitor (ARPI) and to explore clinical characteristics at progression according to TSG status.
View Article and Find Full Text PDFPurpose: This study aimed to investigate the current therapeutic management of patients with early-stage HER2-positive (HER2+) breast cancer in Spain, while also exploring the perceptions surrounding HER2DX in terms of its credibility, clinical relevance, and impact on therapeutic decision-making. Understanding these aspects is crucial for optimizing treatment strategies and enhancing patient outcomes in the context of HER2+ breast cancer.
Methods: An online questionnaire was conducted by an independent third-party between April and May 2022 across 70 medical oncologists highly specialized in breast cancer management in Spain.
Article Synopsis
- Early-stage triple-negative breast cancer (TNBC) has variability in its clinical and biological characteristics, with immune infiltration impacting prognosis, and there’s a need for better genomic tools for treatment decisions.
- This study analyzed genomic and clinical data across seven patient cohorts to evaluate the role of a B-cell/immunoglobulin signature (IGG) in predicting event-free survival (EFS) and overall survival (OS) in TNBC patients.
- Results indicated that IGG is associated with improved EFS and OS, and its integration with tumor staging can help identify patients who may benefit from tailored treatments.
Background: Androgen deprivation therapy (ADT) with docetaxel (D) and/or antiandrogen receptor therapies (ARTs) are the standard therapies in metastatic hormone-sensitive prostate cancer (mHSPC). Alterations in the tumor suppressor genes (TSGs) RB1, PTEN, and TP53 are associated with an aggressive evolution and treatment resistance in castration-resistant prostate cancer (CRPC).
Objective: To study the clinical implications of TSG mRNA expression in mHSPC patients.
Article Synopsis
- Docetaxel is the standard treatment for advanced prostate cancer, but many patients develop resistance due to certain cell signaling pathways becoming overly active.
- This study investigates the combined inhibition of the PI3K/AKT and MEK/ERK pathways in prostate cancer cells that are resistant to docetaxel, showing that this combo treatment can reduce cell growth and promote cancer cell death.
- The results suggest that using selumetinib and AZD8186 together could be a new therapeutic approach for patients with a specific type of docetaxel-resistant prostate cancer, paving the way for future clinical trials.
Importance: Patients with early-stage ERBB2 (formerly HER2)-positive breast cancer (ERBB2+ BC) who experience a pathologic complete response (pCR) after receiving neoadjuvant therapy have favorable survival outcomes. Predicting the likelihood of pCR may help optimize neoadjuvant therapy.
Objective: To test the ability of the HER2DX assay to predict the likelihood of pCR in patients with early-stage ERBB2+ BC who are receiving deescalated neoadjuvant therapy.
Article Synopsis
- Researchers are focusing on the need for biomarkers to enhance the use of pertuzumab in treating early-stage ERBB2-positive breast cancer, moving beyond just ERBB2 status.
- The study aims to evaluate if the HER2DX genomic assay can predict patient responses to trastuzumab-based chemotherapy, with or without pertuzumab, using tissue samples taken before treatment.
- In a retrospective analysis involving 155 patients, the study found significant associations between baseline pCR scores from the genomic assay and the likelihood of achieving a pathologic complete response in breast and axillary tissues.
Article Synopsis
- Liquid biopsy, specifically plasma ctDNA analysis, has potential but its effectiveness in capturing detailed tumor characteristics for clinical use is still being explored.
- In a study with 459 metastatic breast cancer patients, machine learning techniques were applied to ctDNA to uncover complex biological features similar to traditional tumor tissue analysis.
- The research identified four DNA subtypes and a specific ctDNA genomic signature linked to poor treatment response and survival outcomes, highlighting the potential for ctDNA to serve as a valuable predictor in cancer treatment.
In advanced HER2-positive (HER2+) breast cancer, the new antibody-drug conjugate trastuzumab deruxtecan is more effective compared with trastuzumab emtansine (T-DM1). However, trastuzumab deruxtecan can have considerable toxicities, and the right treatment sequence is unknown. Biomarkers to guide the use of anti-HER2 therapies beyond HER2 status are needed.
View Article and Find Full Text PDF(1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX.
View Article and Find Full Text PDFArticle Synopsis
- - The study introduces the HER2DX risk score and pCR score, which utilize a combination of 27 gene expressions and clinical features to predict survival and treatment responses in early-stage HER2-positive breast cancer.
- - HER2DX analyzes factors like tumor size and immune response, using training data from a large cohort of HER2-positive tumors and validating its effectiveness with additional independent cohorts.
- - Results show that the HER2DX risk score is significantly linked to disease-free survival, with low-risk patients having a high 5-year survival rate. Additionally, the pCR likelihood score predicts the likelihood of achieving complete response to treatment with high accuracy.
Altered metabolism is a hallmark of cancer. Malignant cells metabolise glutamine to fulfil their metabolic needs. In prostate cancer, androgen receptor signalling promotes glutamine metabolism, which is also involved in cholesterol homeostasis.
View Article and Find Full Text PDFBackground: Plasma AR status has been identified as a potential biomarker of response in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel or AR-targeted therapies. However, the relevance of plasma AR in the overall management of CRPC patients receiving different docetaxel doses is unknown.
Patients And Methods: This was a multi-institution study of associations between baseline plasma AR copy number status, assessed by droplet digital PCR, and outcome in 325 mCRPC patients receiving docetaxel at standard or adapted regimen at the discretion of the treating physician.
The prostatic tumor cells plasticity is involved in resistance to hormone-therapy, allowing these cells to survive despite androgen receptor inhibition. However, its role in taxanes resistance has not been fully established. Gene expression of plasticity-related phenotypes such as epithelial-mesenchymal transition (EMT), stem cell-like and neuroendocrine (NE) phenotypes was studied , , in circulating tumor cells (CTCs) (=22) and in tumor samples (=117) from taxanes-treated metastatic castration-resistant prostate cancer (mCRPC) patients.
View Article and Find Full Text PDFBackground: Taxanes are the most active chemotherapy agents in metastatic castration-resistant prostate cancer (mCRPC) patients; yet, resistance occurs almost invariably, representing an important clinical challenge. Taxane-platinum combinations have shown clinical benefit in a subset of patients, but the mechanistic basis and biomarkers remain elusive.
Objective: To identify mechanisms and response indicators for the antitumor efficacy of taxane-platinum combinations in mCRPC.
Androgen receptor (AR) signaling remains crucial in castration-resistant prostate cancer (CRPC). Since it is also essential in immune cells, we studied whether the expression of AR full-length and its splicing variant in peripheral blood mononuclear cells (PBMC) predicts systemic treatment response in mCRPC in comparison with circulating-tumor cells (CTC). We measured and mRNA in PBMC and CTC from patients prior to receiving abiraterone (AA), enzalutamide (E), or taxanes by a pre-amplification plus quantitative reverse-transcription PCR.
View Article and Find Full Text PDFBackground: Plasma androgen receptor (AR) copy number status has been identified as a potential biomarker of response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR status in the context of cabazitaxel therapy is unknown.
Patients And Methods: Between September 2011 and January 2018, pretherapy plasma samples were collected from 155 patients treated with second- or third-line cabazitaxel at standard or reduced dose in different biomarker protocols.
TMPRSS2-ERG expression in blood has been correlated with low docetaxel benefit in metastatic castration-resistant prostate cancer (mCRPC). This multicenter study aimed to prospectively asses its role as a taxane-resistance biomarker in blood and retrospectively in tumors, exploring also the impact of prior abiraterone/enzalutamide (A/E) in patients and in vitro. TMPRSS2-ERG was tested by quantitative reverse-transcription PCR.
View Article and Find Full Text PDFPlasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples.
View Article and Find Full Text PDFBackground: Although chemotherapy is the cornerstone treatment for patients with metastatic colorectal cancer (mCRC), acquired chemoresistance is common and constitutes the main reason for treatment failure. Monoclonal antibodies against insulin-like growth factor-1 receptor (IGF-1R) have been tested in pre-treated mCRC patients, but results have been largely deceiving.
Methods: We analysed time to progression, overall survival, and the mutational status of RAS, BRAF and nuclear p-IGF-1R expression by immunohistochemistry, in 470 metastatic CRC patients.
Unlabelled: TMPRSS2-ERG rearrangement is a genetic alteration exclusive to prostate cancer, associated with taxane resistance in preclinical models. Its detection in blood samples of metastatic resistant prostate cancer (mCRPC) patients may indicate the presence of circulating tumour cells with this genetic alteration and may predict taxane resistance. To test this hypothesis, we evaluated TMPRSS2-ERG expression using quantitative reverse transcription polymerase chain reaction in peripheral blood mononuclear cells and tumour tissue from mCPRC patients treated with taxanes.
View Article and Find Full Text PDFProstate cancer is a molecularly heterogeneous disease, and mechanisms of action of taxanes and potential mechanisms of resistance are not clearly defined. Taxanes are microtubule-stabilizing agents resulting in the slowing or blocking of mitosis at the metaphase-anaphase transition and induction of apoptotic cell death. Taxanes also can inhibit androgen receptor pathway.
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