When most people hear “cancer research” they think of experiments on mice, but this long-standing “holy grail” of cancer research is deeply flawed.
Information continues to confirm that using mice for cancer research fails on many levels. While we need look no further than decades of cancer experiments on mice that have not panned out, a new study by researchers at the University of California San Diego revealed key differences between the immune system of mice and humans that have major implications for using immunotherapy.
Immunotherapy has been a game-changer to treat cancer, but still only a fraction of patients benefit from it. Finding out how to treat more patients with immunotherapy is a code that must be cracked.
Cancer immunotherapy is based on targeting the protein PD-1, but the UCSD study found that PD-1 in mice is significantly weaker than human PD-1. This means that the cancer treatments tested on mice do not react the same in humans. Interestingly, it was weaker in mice than in most other mammals, making mice just about the worst choice to study cancer.
Immunotherapy has revolutionized cancer therapy, but human research is needed to expand its use to treat more patients. In today’s newsletter we describe a human study that revealed new insights on immunotherapy, as well as some recent breakthroughs in cancer research that have come entirely from human-centered research. Experiments on mice or other animals simply cannot provide this level of human-relevant information.
Researchers build first large-scale atlas of how immune cells react to mutations during cancer immunotherapy
A
study of human patients led by the Cleveland Clinic and Bristol Myers Squibb has resulted in new insights into how the immune system affects tumors when exposed to immunotherapy.
Researchers used samples of patients’ tumors and blood sampling to analyze mutations and response to immunotherapy. Using high-throughput T-cell profiling and AI, they tracked changes in neoantigens before and after receiving immunotherapy. Neoantigens are peptides produced by mutated cancer cells that alert the immune system to the presence of a tumor.
According to Timothy Chan, MD, Chair of Cleveland Clinic's Global Center for Cancer immunotherapy, "Learning why our immune systems respond to some cancerous mutations but not others is like the holy grail for immunotherapy researchers. Our findings are one of the closest things we have to figuring these things out."
Pancreatic Cancer Protein Targeted by Protein Degraders
Pancreatic cancer has been difficult to treat because of a highly fibrous tissue that covers pancreatic cancer cells, blocking treatments from reaching them.
In a
new animal-free study from the University of California Riverside, researchers used human cancer cell lines to identify protein degraders that can target a key protein known as Pin1 which is involved in the development of pancreatic cancer.
The scientists discovered inhibitors that can bind to the Pin1 protein and kill cancer-associated fibroblasts. These findings show promise to develop treatments that can reach pancreatic cells and improve outcomes for pancreatic cancer patients.
Algorithm Exposes Cells Driving Aggressive Tumor Growth
Scientists at the University College London and The Francis Crick Institute
developed a sophisticated algorithm that can quickly analyze individual cells in a tumor to find those growing the fastest.
Their analysis of 15,000 cancer cells from a lung cancer donor showed that the fastest growing cells were those spreading the cancer to other parts of the body and entering the bloodstream. This points towards a potential blood test that could identify the aggressive cells and allow scientists to target them.
Dr. Simone Zaccaria, senior author, states “Future progress in cancer research hinges on the use of cutting-edge technologies to pave the way for more precise interventions and better patient outcomes.”
Tongue cancer organoids reveal secrets of
chemotherapy resistance
Tongue cancer is the most common type of oral cancer, which is increasingly prevalent worldwide. Recurrence rates are high because just a few surviving cells after chemotherapy can maintain the cancer.
To better understand why this happens, scientists at the Institute of Science Tokyo
developed tongue cancer organoids using tissue samples from 28 patients to accurately model human tongue cancer.
They used the tongue organoids to conduct comprehensive and comparative analyses and found that chemotherapy drugs caused cancer cells to enter a dormant-like state. Next, they obstructed these pathways with specific inhibitors and saw that the chemo-resistant cells became sensitive to chemo. This indicates that using such inhibitors to treat tongue cancer patients could be a highly impactful therapeutic target. This human-relevant study is one more example of how animal-free research can advance cancer treatment.
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