Triple-negative breast cancer can be treated with a new treatment

Spanish researchers have achieved a significant breakthrough in the fight against the deadliest form of breast cancer—triple-negative breast cancer (TNBC). This aggressive subtype’s high rate of relapses and metastasis makes treatment particularly challenging. The team from the Cancer Center Clínica Universidad de Navarra (CCUN) has developed a promising therapeutic approach that halts metastasis and eradicates tumour relapse in preclinical models.

The key to their success lies in targeting a molecule known as ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1). ENPP1 has a key role in the tumor’s ability to evade immune systems and spread to different parts of the body. The researchers found that by pharmacologically blocking ENPP1, they were able enhance the effects radiotherapy and reduce tumour recurrence in lab models.

The incidence of triple-negative cancer is approximately 15-20%, but the disease causes disproportionately more deaths than other breast cancers due to its aggressiveness and absence of targeted treatments. TNBC, unlike other breast cancer types lacks receptors that are sensitive to oestrogen or progesterone. Due to this, the treatment options are limited, and often radiotherapy or chemotherapy is used, which has a high rate of failure. The Spanish researchers’ study demonstrated that blocking the ENPP1 receptor makes TNBC tumors more susceptible to radiotherapy. This inhibition restores the immune system’s ability to identify and attack cancerous tumour cells. This process is suppressed when aggressive tumours are present. The treatment reduced the frequency of metastases in breast cancer by preventing cancer cells from escaping immune detection.

The researchers evaluated the therapy on preclinical animals and noted a reduction in tumour relapses and metastatic burden. This suggests that radiotherapy and ENPP1 inhibitors could be a novel treatment for TNBC patients. This discovery could have significant implications for future treatment of triple-negative cancer. TNBC patients have a poor outlook, and new therapies are urgently needed to improve their quality of life and survival. This approach targets two major factors for the progression of disease and treatment resistance: immune evasion and metastasis.

The findings were published in a peer-reviewed Journal Signal Transduction Therapy and Targeted TherapyThe publication highlights the importance of translational research that moves promising laboratory discoveries toward clinical application. This publication highlights the importance of translating promising laboratory discoveries into clinical applications. Next, clinical trials will evaluate the safety of ENPP1 inhibitors combined with radiotherapy for human patients. If these trials are successful, this treatment could be a new standard for treating triple-negative cancers, giving hope to thousands of women worldwide.

This progress also reflects Spain’s increasing role in cancer research at the cutting edge and its commitment to develop innovative treatments. Spanish scientists have contributed valuable knowledge to cancer treatment by focusing on the molecular target and tumour microenvironment.

Conclusion: The inhibition of ENPP1 represents a promising frontier in the fight against breast cancer’s deadliest subtype. By preventing tumour cells from evading the immune system and enhancing radiotherapy’s effectiveness, this strategy offers a potential pathway to reduce metastasis and prevent relapse—key challenges in improving patient outcomes. Patients and healthcare providers can be hopeful as research moves from the lab to the clinical setting. This breakthrough could lead to targeted, more effective treatments for triple negative breast cancer.