A study conducted at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau suggests that certain microRNAs (miRNAs) may be useful as non-invasive biomarkers for the early diagnosis of lymph node metastasis in patients with early-stage breast cancer. The research, led by Dr. Agustí Barnadas, head of the Clinical Oncology research group at IIB Sant Pau and head of the Medical Oncology service at the same hospital, focused on patients with early-stage breast cancer with estrogen receptor-positive (ER-positive) tumors.
MiRNAs are small RNA molecules that play a crucial role in gene expression regulation and have been linked to different stages of the metastatic process. One particularly intriguing aspect of miRNAs is their stability in peripheral blood, making them ideal candidates to be biomarkers using non-invasive techniques such as a blood sample.
The study, which had a proof-of-concept approach, included 30 patients with early-stage breast cancer for whom plasma samples, sentinel lymph nodes, and tumor tissue samples were available. The researchers performed RNA sequencing on these samples and conducted differential expression analysis, gene ontology, and enrichment analysis.
The results of the study revealed that circulating miRNAs showed inverse expression compared to tumor tissue or sentinel lymph nodes obtained from the same patients. Overall, there was a trend toward downregulation of circulating miRNAs. However, two miRNAs, miR-643a-3p and miR-223, were highlighted, showing increased expression in patients with positive sentinel lymph nodes, suggesting a potential link to the presence of lymph node metastasis.
Additionally, the researchers observed significant enrichment of biological processes related to the regulation of epithelial cell proliferation and transcriptional regulation, processes associated with metastasis promotion.
These results indicate the potential role of various circulating miRNAs as markers of axillary lymph node involvement in patients with early-stage breast cancer.
As explained by Dr. Barnadas, this advancement in breast cancer research not only offers new perspectives for the early diagnosis of metastasis but also raises the possibility of designing stricter monitoring strategies or clinical studies to explore the value of new therapies.
Cancer Research at Sant Pau On the occasion of World Cancer Research Day on September 24th, Dr. Barnadas highlights that the Sant Pau Research Institute currently has more than 200 ongoing clinical trials in cancer with active recruitment, and about 15 in the Phase I trial unit of Onco-Hematology.
This expert believes that one of the main goals of cancer research at present is to find mechanisms to trigger immune responses against tumors. In this regard, Dr. Javier Briones, director of the Cellular Immunotherapy and Gene Therapy Research Group at IIB-Sant Pau and head of the Clinical Hematology Unit at Sant Pau Hospital, has developed a new immunotherapy drug, CAR-T 19, which is being administered in a clinical trial to patients with certain types of lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma) that have not responded to other treatments. It is the second academic advanced therapy medicinal product produced and developed entirely at Sant Pau.
Moreover, in 2020, the first trial with a CAR-T immunotherapy drug in Europe began for the treatment of classic Hodgkin lymphoma and CD30+ non-Hodgkin T-cell lymphoma in relapse or refractory cases.
The initial results of this study were presented last year at the most prestigious international Hematology congresses, and it is currently in Phase II. It represents the first CAR-T30 immunotherapy drug (academic), fully produced at Sant Pau, attracting patients from various countries, including Italy, Austria, Poland, Russia, among others.
“This is an area of research that has made significant progress in recent years in the treatment of onco-hematological diseases, but we hope that it will also have an important role in solid tumors in the future,” Dr. Barnadas comments.
Another strong focus in oncology research is the genetic characterization of tumors. Recently, Dr. José Pablo Maroto, a researcher from the Clinical Oncology Group at IIB Sant Pau and an oncologist at the same hospital, found very rare mutations in the USP9X protein, which regulates critical cellular processes for tumor growth, in a study conducted in collaboration with the National Center for Oncological Research (CNIO).
This discovery arose from the case of a patient with metastatic kidney cancer who was treated with the drug temsirolimus, which worked much better than expected. The patient successfully overcame cancer. Nine years later, she was diagnosed with bone metastasis, but once again, temsirolimus proved effective.
“Collaboration with many other centers is essential to generate knowledge and develop new therapeutic strategies that can decisively advance in the fight against cancer,” Dr. Barnadas emphasizes.
According to this expert, one of the major challenges in cancer research today is recognizing the mechanisms of resistance that develop during treatment to make a tumor stop responding to a specific treatment at a certain point.
“This is a challenge in oncology in general because patients with disseminated disease, despite initially showing very good responses to targeted treatments, eventually develop resistance. Being able to identify it early and having tools to reverse it can lead to better results in the medium or long term.”
Another challenge is to better understand the mechanisms involved in the host’s immune response against the disease. “Here, we need to make more progress to achieve better results, where immunotherapy alone or in combination with chemotherapy and other strategies can achieve a better and longer-lasting effect. Often, you can observe significant results in advanced disease, but the patient, after a few years, develops the disease again, and at that point, you have no option for immunotherapy treatment or to try to reverse it, but the strategies are less effective,” as Dr. Barnadas indicates.
A third challenge in cancer research, according to this expert, is early identification “not only of resistance but also of disease relapse through new strategies such as liquid biopsy.”
Finally, Dr. Barnadas has emphasized the importance of not lowering the guard to further promote early cancer diagnosis and to determine the patient profile more precisely to decide who is a candidate for specific screening studies.
Reference article
Escuin D, López-Vilaró L, Bell O, Mora J, García-Valdecasas B, Moral A, Clos M, Boronat L, Arqueros C, Barnadas A. Circulating miRNA Expression Is Inversely Correlated with Tumor Tissue or Sentinel Lymph Nodes in Estrogen Receptor-Positive Early Breast Cancer Patients. Int J Mol Sci. 2023 Aug 27;24(17):13293. doi: 10.3390/ijms241713293. PMID: 37686099; PMCID: PMC10487825.
