Prodrugs in Oncology: Teaching Old and New Drugs More Tricks

Jane De Lartigue, PhD
Published: Tuesday, Nov 06, 2018
For decades, investigators have been looking for ways to combine the optimal aspects of different types of anticancer therapy to create more effective, safer drugs. As researchers gain a better understanding of the unique aspects of individual tumor types and their surrounding microenvironment, the design of novel therapies categorized as prodrugs is become increasingly sophisticated, and several novel constructs show particular promise.

Prodrug: A Broad Label

The term prodrug was coined in the 1950s3 and has been explored as a drug design strategy ever since. It refers to an inactive or less active derivative of a drug molecule that can be transformed into the active form via some sort of chemical or enzymatic activity.

Figure. Antibody-Drug Conjugates in Action8

Antibody-Drug Conjugates in Action

Antibody-Drug Conjugates

ADCs represent the most promising form of prodrug therapy to date. They are composed of a monoclonal antibody that targets a specific tumor-associated antigen linked to a chemotherapeutic agent, which, in theory, enables targeted delivery of the cytotoxic “payload” to the tumor (Figure).

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Less Conventional Chemotherapy

ADCs are an example of a carrier-linked prodrug, wherein the parent drug itself is not modified but attached to a secondary molecule that dictates its activity. Alternatively, prodrugs can involve specific alterations to the parent drug.
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Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
Oncology Briefings™: Individualizing Treatment After Second-Line Therapy for Patients With mCRCAug 29, 20191.0
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