The discovery of cancer drugs that can reverse changes in the brain associated with Alzheimer’s disease has brought new hope to researchers. Scientists at UC San Francisco and Gladstone Institutes have identified two cancer medications, letrozole and irinotecan, which showed surprising potential in reversing Alzheimer’s symptoms.

These scientists first analyzed gene expression data from human brain cells affected by Alzheimer’s, then compared it with the effects of thousands of existing drugs on gene expression. They found that just 10 out of 1,300 drugs reversed the Alzheimer’s disease gene expression signature in one cell type or several cell types in the brain. These 10 drugs had already been approved by the FDA for use in humans.

Poring through electronic medical records housed in the UC Health Data Warehouse, which includes anonymized health information on 1.4 million people over the age of 65, the researchers found that several of these drugs seemed to have reduced the risk of developing Alzheimer’s disease over time.

The team chose letrozole and irinotecan for laboratory testing, predicting one would remedy Alzheimer’s in neurons and the other would help glia. They used a mouse model of aggressive Alzheimer’s disease with multiple disease-related mutations.

When tested together, these two cancer drugs reversed multiple aspects of Alzheimer’s in the animal model, including undosable gene expression signatures in neurons and glia that had emerged as the disease progressed. The combination reduced brain degeneration, and importantly, restored memory.

The research has sparked excitement among scientists, who hope this can lead to a real solution for millions of patients with Alzheimer’s disease. A clinical trial is expected soon to directly test the combination therapy in Alzheimer’s patients.

The breakthrough was made possible by analyzing single-cell gene expression data from brain cells affected by Alzheimer’s and comparing it with existing medical records and data on thousands of drugs’ effects on gene expression.

Scientists are hopeful that this can be swiftly translated into a real solution for millions of patients with Alzheimer’s disease, offering new hope in reversing the relentless decline in cognition, learning, and memory associated with the condition.

The UC Davis Comprehensive Cancer Center has made a groundbreaking discovery that may explain why certain immune cells in humans are less effective at fighting solid tumors compared to non-human primates. This finding could lead to more powerful cancer treatments.

Researchers have uncovered an evolutionary change that makes the Fas Ligand (FasL) protein, essential for triggering programmed cell death and killing cancer cells, vulnerable to being disabled by plasmin in humans. This genetic mutation is unique to humans and not found in non-human primates, such as chimpanzees.

“The evolutionary mutation in FasL may have contributed to the larger brain size in humans,” said Jogender Tushir-Singh, senior author for the study and an associate professor in the Department of Medical Microbiology and Immunology. “But in the context of cancer, it was an unfavorable tradeoff because the mutation gives certain tumors a way to disarm parts of our immune system.”

The team discovered that a single evolutionary amino acid change – serine instead of proline at position 153 – makes FasL more susceptible to being cut and inactivated by plasmin. Plasmin is often elevated in aggressive solid tumors, such as triple negative breast cancer, colon cancer, and ovarian cancer.

This means that even when human immune cells are activated and ready to attack the tumor cells, one of their key death weapons – FasL – can be neutralized by the tumor environment, reducing the effectiveness of immunotherapies. The findings may help explain why CAR-T and T-cell-based therapies often fall short in solid tumors.

Blood cancers often do not rely on plasmin to metastasize, whereas tumors like ovarian cancer heavily rely on plasmin to spread the cancer.

Significantly, the study also showed that blocking plasmin or shielding FasL from cleavage can restore its cancer-killing power. This finding may open new doors for improving cancer immunotherapy.

By combining current treatments with plasmin inhibitors or specially designed antibodies that protect FasL, scientists may be able to boost immune responses in patients with solid tumors.

“Humans have a significantly higher rate of cancer than chimpanzees and other primates,” said Tushir-Singh. “There is a lot that we do not know and can still learn from primates and apply to improve human cancer immunotherapies.”

A groundbreaking clinical trial has revealed that a single dose of psilocybin, a naturally occurring psychedelic compound found in mushrooms, can provide sustained reductions in depression and anxiety in individuals with cancer suffering from major depressive disorder. The findings, published in the peer-reviewed journal CANCER, suggest that this treatment approach may offer long-term relief for cancer patients struggling with depression.

The study involved 28 participants who received psychological support from a therapist prior to, during, and after receiving a single 25-mg dose of psilocybin. Two years later, a significant proportion of these individuals demonstrated lasting reductions in depression and anxiety. Specifically:

* 53.6% (15 patients) showed a sustained reduction in depression.
* 50% (14 patients) experienced remission from depression as well as reduced anxiety.
* 42.9% (12 patients) reported reduced anxiety at the two-year mark.

Building on these promising results, an ongoing randomized, double-blind trial is currently evaluating up to two doses of 25 mg of psilocybin versus placebo for treating depression and anxiety in cancer patients. This study aims to determine whether repeating the treatment can resolve depression for more than half of the participants.

According to lead author Manish Agrawal, MD, from Sunstone Therapies, “One dose of psilocybin with psychological support has a long-term positive impact on relieving depression for as much as 2 years for a substantial portion of patients with cancer. If randomized testing shows similar results, this could lead to greater use of psilocybin to treat depression in patients with cancer.”