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Building Targeted Chemotherapies: ADCs, ProTides And ‘Click Chemistry’

 
• By Ben Comer

If targeted therapies for cancer represent a more precise, laser-like attack on solid tumors and blood cancers, cytotoxic chemotherapies are more like a ham-fisted boxer punching every cell in sight. New methods for delivering chemotherapy directly into cancer cells may help to improve efficacy and reduce – or eliminate – damaging and sometimes deadly side effects.    

Howard Skipper, early cancer chemotherapy researcher
Early Chemotherapy Researcher Howard Skipper

Antibody-drug conjugates (ADCs), which pair a chemotherapy agent with a monoclonal antibody using a chemical linker, are designed to target a specific antigen present on the surface of cancer cells. This approach aims to circumvent the fundamental problem with chemotherapies, which is the damage they can do to healthy, noncancerous cells. Chemotherapy’s destruction of healthy cells can trigger a long list of adverse events, from hair loss, fatigue and nausea, to peripheral neuropathy, cognitive disfunction and heart failure.

Research and development of ADCs for cancer is a growing sector of activity; after Wyeth’s (now Pfizer’s) Mylotarg (gemtuzumab ozogamicin) was approved in 2000, for CD33-positive acute myeloid leukemia (AML),...

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