1. Biomarkers of Resistance and Sensitivity to Treatment in HER2-Positive Breast Cancer. This line focuses on understanding the tumor heterogeneity of HER2-positive breast cancer to optimize treatment responses. The goal is to identify patients who may benefit from intensive therapies and those who can avoid unnecessary treatments, and their associated toxicity (Pernas S, et al Front Oncol 2019). Collaborations with IDIBAPS and Hospital Clínic support the validation of the HER2DX, the first prognostic assay for this subtype of breast cancer. Ongoing studies explore early on-treatment biopsies, spatial transcriptomics, and radiomics to improve the prediction of pathological complete response (pCR).
2. Molecular Characterization of Metaplastic Breast Cancers. Given the poor prognosis and heterogeneity of metaplastic tumors, this research line investigates their mutational landscape and tumor evolution through sequencing studies and patient-derived xenograft models. These efforts aim to enhance our understanding of metaplastic breast cancer biology and assess responses to novel therapeutic strategies.
3. Neoadjuvant Hormonal Treatment. This line investigates predictive and prognostic factors for neoadjuvant hormone therapy, which has shown a 50% clinical response rate and improves breast-conserving surgery rates with reduced toxicity. The combination of targeted therapies with hormonal treatment is also explored to enhance therapeutic efficacy.
4. Optimizing Axillary Management. Through a multidisciplinary approach,we aim to balance oncological safety with treatment de-escalation to improve patient quality of life. The ADARNAT trial (García-Tejedor et al., 2023) compares axillary lymph node dissection vs. radiotherapy in SLN-positive patients after neoadjuvant therapy, supporting less invasive strategies. Additionally, García-Tejedor et al. (2023) analyze axillary management in postmenopausal cN0 HR+/HER2- patients treated with neoadjuvant endocrine therapy, highlighting tailored approaches.
5. CRISPR Screening in Breast Cancer. Utilizing CRISPR-based genomic screens with both commercial and custom-designed libraries, this line aims to identify critical genes involved in breast cancer progression. Building on extensive expertise in RNA interference and gene-editing technologies, the group seeks to uncover novel therapeutic targets for breast cancer.
6. Protein Glycosylation in Breast Cancer. Abnormal glycosylation patterns are frequently observed in breast cancer, correlating with tumor growth, invasion, immune evasion, and therapeutic resistance. To investigate this, our group has developed a custom CRISPR library targeting all known glycosylation-related genes. By systematically interrogating these genes, we aim to identify those essential for breast cancer development, providing a deeper understanding of the disease and uncovering potential therapeutic targets.
7. Role of S100A9 in Breast Cancer. Through a whole-genome shRNA screen, we identified the JAK2/STAT3/S100A9 axis as a critical and activated pathway essential for the growth of HER2+ breast tumors. Current research focuses on elucidating the molecular mechanisms driven by S100A9, its interaction with the tumor microenvironment, and its potential as a biomarker and therapeutic target for aggressive breast cancer.
8. Regulation of Mammary Gland Development and Breast Cancer by microRNAs. This line explores the role of the miR-424/503 cluster in mammary gland involution, treatment resistance, and Wnt signaling modulation. Given the growing relevance of RNA-based therapies, the group continues to investigate how microRNAs influence tumor progression and therapy resistance.
