Paul Ehrlich's magic bullet concept: 100 years of progress

Abstract

Exceptional advances in molecular biology and genetic research have expedited cancer drug development tremendously. The declared paradigm is the development of 'personalized and tailored drugs' that precisely target the specific molecular defects of a cancer patient. It is therefore appropriate to revisit the intellectual foundations of the development of such agents, as many have shown great clinical success. One hundred years ago, Paul Ehrlich, the founder of chemotherapy, received the Nobel Prize for Physiology or Medicine. His postulate of creating 'magic bullets' for use in the fight against human diseases inspired generations of scientists to devise powerful molecular cancer therapeutics.

The potential legacy of cancer nanotechnology: cellular selection

“…The nanotechnology-based approach can selectively target P-gp to stop drug clearance [I and ii]; the local concentration of the drug can be increased due to the positive enhanced permeability and retention (EPR) effect and the amount of drug delivered by the nanocarrier [iii]; a combinatorial drug delivery system can be used for delivery of multiple drugs simultaneously to avoid clearance of all drug molecules [iv]. In MDR, p53 alters apoptotic signalling molecule Bcl-2 and cell cycle regulatory molecule microtubule-associated protein (MAP)4 [4]. The release of transcription factor E2F regulates drug sensitivity (e.g., methotrexate, and fluorouracil etc) by producing dihydrofolate reductase (DHFR) and thymidylate synthetase (TS).…”

“…Multiplex nanoparticles with all the required functionalities for cancer management may be the way to realise the 'magic bullet' proposed 100 years ago by Paul Ehrlich to treat cancer [4]. …”

“…In 1906, Paul Ehrlich coined the term "magic bullet" to describe the ideal therapeutic reagent, possessing excellent targeting ability with super specificity [4]. Despite the many thousands of research articles that have since been published on drug targeting, this vision has remained an elusive goal in clinical practice.…”

Self‐Triggered Apoptosis Enzyme Prodrug Therapy (STAEPT): Enhancing Targeted Therapies via Recurrent Bystander Killing Effect by Exploiting Caspase‐Cleavable Linker

“…Thus, many different classes of targeted therapies are being developed and used clinically 1. Examples include antibodies, tyrosine kinase inhibitors (TKI), antibody–drug conjugates (ADC), and enzyme prodrug therapies (EPT) 1, 2.…”

An Intravascular Magnetic Catheter Enables the Retrieval of Nanoagents from the Bloodstream

“…The dream of all nanomedicine approaches is to develop the so‐called Ehrlich's “Magic Bullet,”7, 8 i.e., a drug that selectively attaches to diseased cells but nontoxic to healthy ones. Many efforts have been devoted toward the development of nanovectors able to efficiently disperse therapeutic molecules in their structures, to guarantee a favorable blood half‐life, and to minimize the immune system response 9.…”