Two studies out of the La Jolla institution use AI and bioengineering to promote destruction of cancer cells, which could lead to better cancer treatment.
Scientists at UC San Diego have developed a new approach to destroying cancer stem cells, which are hard to find and help cancers spread, return after treatment and resist therapy. The approach, tested in colon cancer, leveraged artificial intelligence to reprogram cancer stem cells, ultimately triggering them to self-destruct.
Because it only targets cancer cells without affecting surrounding tissues, the approach could be a safer and more precise alternative to current therapeutic approaches.
The results, published Oct 20 in Cell Reports Medicine, also demonstrate the transformative potential of human-based, non-animal research methods.
The research team outsmarted the elusive cancer cells by building a machine learning tool called CANDiT (Cancer Associated Nodes for Differentiation Targeting) to identify new treatment targets for a specific tumor based on its unique genetics.
The tool, starting with a single key gene, identifies a network of genes related to the initial gene, suggesting treatment targets that can revert the cells to a healthier state.
In the study, the team’s approach led to the identification of a protein called PRKAB1, which helps cells respond to stress. By using an existing drug that activates this protein, the researchers were able to restore function of a significant gene in colon cancer stem cells.
After treatment, the cancer stem cells began to behave more like normal healthy cells, but this isn’t all that happened.
“What surprised us most was that after we reprogrammed the cancer stem cells to behave like normal cells, they chose to self-destruct instead,” first author Saptarshi Sinha, PhD, interim director of the Center for Precision Computational Systems Network (PreCSN), part of the Institute for Network Medicine (iNetMed) at the UCSD School of Medicine, said in a press release.
To demonstrate the clinical potential of this approach, the researchers were able to leverage UC San Diego’s HUMANOID Center, also part of iNetMed, to successfully test the drug in patient-derived organoids — tiny, lab-grown replicas of human tumors that allow researchers to safely and effectively test treatments in human tissues.
The research indicates great potential to reduce the risk of recurrence and death in colon cancers.
A different study, published Oct 13 in Molecular Cancer Therapeutics, revealed UCSD School of Medicine researchers’ success in developing a new approach to treating advanced cancers that have become resistant to treatment.
The research team took advantage of a tumor’s own immune landscape, engineering a new anti-αvβ3 antibody (αvβ3 is a protein driving treatment resistance and metastasis) that triggered powerful anti-tumor responses in both patient tumor samples and in mouse models.
The new antibody killed cancer cells more effectively than the older version, leading to increased tumor cell death and reduced tumor growth, among other results, suggesting that customizing antibody therapies to target the dominant immune cells present in a given tumor could dramatically improve outcomes for patients with aggressive, drug-resistant cancers.
