Antibody-drug conjugates are targeted cancer therapies. They deliver potent drugs directly into cancer cells while minimizing harm to healthy tissue. These therapies work by recognizing specific proteins found on the surface of cancer cells.

The proteins function like a lock and the therapy acts as a key, latching onto the cancer cells with precision to deliver the treatment.

But precision alone isn’t enough. Even when the key fits the lock, the door often stays closed. This prevents the drug from entering the cell to attack the cancer. 

Now, Mayo Clinic researchers have developed a pioneering strategy that may help overcome this barrier. The approach combines antibody-drug conjugates with proteolysis-targeting chimeras. These molecular tools break down specific proteins to improve how cancer cells internalize the cancer-fighting therapy.  

In a preclinical study, published in Communications Biology, the combined therapy improved the internalization of these treatments by up to 1.9 times in certain models.  

"The ability to target specific proteins and improve drug absorption into tumor cells represents a significant step forward in how we approach aggressive cancers," says Aaron Mansfield, M.D., a medical oncologist and lead author of the study at the Center for Individualized Medicine and the Mayo Clinic Comprehensive Cancer Center. 

Dr. Mansfield and his team tested the approach using breast cancer organoids. They created these miniaturized, lab-grown versions of breast tissue to mimic the complexity of real tumors. Unlike traditional cell cultures, organoids better replicate how tumors behave in the body.

Specifically, the research focused on three proteins often found in aggressive cancers. These include human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and mesenchymal-epithelial transition factor (MET). These proteins are associated with breast, lung and pancreatic cancers.  

Overall, the study highlights the versatility of this approach by demonstrating potential benefits across multiple cancer types and protein targets. 

For a complete list of authors, disclosures and funding, review the study. 

Other recent research from Dr. Mansfield

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