Medical Bulletin 04/ April/ 2025 - Video

Linoleic acid, an omega-6 fatty acid enhanced the growth of the hard-to-treat “triple negative” breast cancer subtype, according to a preclinical study led by Weill Cornell Medicine investigators.

In the study, published in Science, the researchers found that linoleic acid can activate a major growth pathway in tumor cells by binding to a protein called FABP5. Comparing breast cancer subtypes, the team observed that this growth pathway activation occurs in triple-negative tumor cells, where FABP5 is particularly abundant, but not in other hormone-sensitive subtypes. In a mouse model of triple-negative breast cancer, a diet high in linoleic acid enhanced tumor growth.

Researchers looked at the ability of omega-6 fatty acids—particularly linoleic acid to drive an important, nutrient-sensing growth pathway called the mTORC1 pathway.

A key initial finding was that linoleic acid does indeed activate mTORC1 in cell and animal models of breast cancers, but only in triple-negative subtypes. The scientists discovered that this subtype-specific effect occurs because the polyunsaturated fatty acid forms a complex with FABP5, which is produced at high levels in triple-negative breast tumors but not in other subtypes, leading to the assembly and activation of mTORC1, a major regulator of cell metabolism and cancer cell growth.

Feeding mice that model triple-negative breast cancer a high-linoleic-acid diet increased FABP5 levels, mTORC1 activation and tumor growth. The researchers also found increased levels of FABP5 and linoleic acid in the tumors and blood samples from newly diagnosed triple-negative patients.

The illumination of FABP5’s importance in this process suggests, moreover, that it could be a good “biomarker” to guide more personalized nutritional and therapeutic interventions for patients with triple negative breast cancer, which currently lacks any targeted therapy.

Reference: Nikos Koundouros et al., Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling.Science387,eadm9805(2025).DOI:10.1126/science.adm9805

According to a letter published in Nature Medicine, Mpox has the potential to become a significant global health threat if taken too lightly, according to scientists at the University of Surrey.

Researchers highlighted how mpox – traditionally spread from animals to humans – is now showing clear signs of sustained human-to-human transmission.

Mpox is a viral infection caused by a virus that belongs to the same family as smallpox. The virus can cause a painful rash, fever, and swollen glands and, in some cases, lead to more serious illness. Mpox usually spreads through close contact with an infected person or animal.

The article notes that this change coincided with the rapid spread of clade IIb (a clade is a group of viruses that share a common ancestor) mpox viruses, but different clade I variants are now on the rise too. Researchers are also concerned because clade I viruses are thought to be more aggressive. These viruses appear to be accumulating specific genetic mutations – driven by enzymes in the human body – that may be changing viral properties, so the longer these viruses circulate amongst us, the higher the chances these mutations help mpox adapt to humans.

Carlos Maluquer de Motes, Reader in Molecular Virology at the University of Surrey, said:

“The most recent outbreaks show that intimate contact is now a significant way the virus spreads. That shift in how it’s transmitted is leading to longer transmission chains and lasting outbreaks.”

“Mpox control has to climb up the global health agenda. We have limited diagnostic tools and even fewer antiviral treatments. We urgently need better surveillance and local or regional capacity to produce what we need – otherwise, we are at risk of future epidemics.”

Unlike smallpox, mpox has an animal reservoir, meaning it can’t be fully eradicated. The authors warn that unless international action is taken now – including investment in point-of-care testing and new treatments – mpox will continue to re-emerge and threaten global health.

Reference: Maluquer de Motes, C., Ulaeto, D.O. Mpox poses an ever-increasing epidemic and pandemic risk. Nat Med (2025). https://doi.org/10.1038/s41591-025-03589-8

A new form of tumor infiltrating lymphocyte therapy, a form of personalized cancer immunotherapy, improved the treatment’s effectiveness in patients with metastatic gastrointestinal cancers, according to results of a clinical trial published in Nature Medicine

This therapy could be used to treat a variety of solid tumors, which has so far eluded researchers developing cell-based therapies.

This form of therapy involves identifying and selecting immune cells that are found in the tumor that specifically recognize and attack a patient’s tumor cells. Next, scientists grow those tumor infiltrating lymphocyte into large quantities in the laboratory before they are finally administered to the patient.

Patients in the clinical trial, who had a variety of gastrointestinal tumors, also received the immune checkpoint inhibitor pembrolizumab (Keytruda) to help further boost their immune response. The result was nearly 24% of patients treated with selected tumor infiltrating lymphocyte plus pembrolizumab had a substantial reduction in the size of their tumors, compared with 7.7% of patients who received selected tumor infiltrating lymphocyte without pembrolizumab. Patients treated with tumor infiltrating lymphocyte that had not been selected for anti-tumor activity had no tumor shrinkage.

The clinical trial included 91 patients with metastatic gastrointestinal cancers—including esophageal, stomach, pancreatic, colon, and rectal cancers—that had worsened despite a median of four prior treatment regimens. In the pilot phase of the trial, 18 patients were treated with tumor infiltrating lymphocyte that had not been selected for anti-tumor activity, and there were no objective responses. In the second phase, 39 patients were treated with selected tumor infiltrating lymphocyte therapy, and 7.7% had objective responses.

In the third phase, 34 patients received pembrolizumab immediately before selected tumor infiltrating lymphocyte therapy. This group had the best response, with 23.5% patients experiencing an objective response. All 91 patients had also received standard chemotherapy and high-dose interleukin-2 before the tumor infiltrating lymphocyte therapy.

In the trial’s second and third phases, objective responses were seen in multiple types of gastrointestinal cancers, including cancers of the colon, rectum, pancreas, and bile duct. Responses lasted between 8 months and more than 5.8 years in the group that received selected tumor infiltrating lymphocyte therapy alone, and between 4 months and 3.5 years in the group that received selected tumor infiltrating lymphocyte therapy and pembrolizumab. Serious side effects occurred in 30% of patients treated with selected tumor infiltrating lymphocyte.

Reference: Lowery, F.J., Goff, S.L., Gasmi, B. et al. Neoantigen-specific tumor-infiltrating lymphocytes in gastrointestinal cancers: a phase 2 trial. Nat Med (2025). https://doi.org/10.1038/s41591-025-03627-5