Despite the continuing development of new and more efficient treatments, cancer remains the second cause of premature death worldwide. Multi-faceted interdisciplinary research efforts in industry and academia on different aspects of cancer have provided a knowledge basis for the development of novel therapeutic approaches.
Paul Ehrlich, Nobel laureate in Physiology of 1908, had the early vision that a compound could be made to selectively target a disease-causing organism or tumour. The European Training Network (ETN) Magicbullet::Reloaded refers to Ehrlich's visionary concept and focused on the development of new-generation anticancer agents, capable of selectively eradicating cancer cells, while sparing healthy tissues. The consortium thus addressed important societal challenges and specific concerns shared by citizens in Europe in terms of health and well-being. Efforts are required to maintain effective healthcare for all ages. New, efficient and sustainable therapies against complex diseases, such as cancer, and stratified and/or personalised treatments need to be developed. The ETN Magicbullet::Reloaded brought together academic and industrial partners, both larger companies and SME, from six different countries. There is expertise in Organic Chemistry, Peptide Chemistry, Medicinal Chemistry, Drug Discovery, Biochemistry, Pharmacology and Cell Biology. Fifteen Early-Stage Researchers, recruited for the project, were trained in an interdisciplinary context for a future employment in pharmaceutical research and development.
In targeted tumour therapy, an antitumour agent should be delivered specifically at the site of disease. Such an ideal therapeutic agent would be a “magic bullet” that is directed only to the site of pathology, because it is carrying a chemical “address label”. Thus, higher treatment efficiency is to be expected without adverse side effects observed in classical tumour therapy.
Several antibody-drug conjugates (ADC) have been approved during the past two decades. On its way to the tumour, an antitumour agent needs to cross barriers in the body. Once arrived at a solid tumour, it should be capable to penetrate into the tumour tissue. However, ADC often are compromised by insufficient tissue penetration. Conversely, small molecule-drug conjugates (SMDC) easily are able to diffuse into tumour tissue because of the smaller size.
The ETN Magicbullet::Reloaded consortium carried out the synthesis and biological evaluation of small molecule-drug conjugates (SMDC) and antibody-drug conjugates (ADC). The conjugates comprise a tumour-targeting unit (e.g. a small molecule, a peptide, or an antibody) and an anticancer drug (i.e. a cytotoxic or immune-stimulating agent, also called payload), connected by a suitable linker-spacer system. Binding of the targeting unit to tumour-associated receptors promotes the accumulation of the payload at the tumour site. The linker-spacer system is fundamental for the release of the drug in its active form at the tumour site, while premature drug release in the blood stream has to be prevented. Focus was also being placed on drugs capable to stimulate tumour immune responses and overcome resistance to immuno-therapy.
