Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Mechanisms of carcinogenesis and their role in anti-cancer drug approvals via the EU centralised procedure (1995–2009) ***

Dr. Annika Brendle (Abschlußjahr: 2013)

Summary

Cancer which represents the second most common cause of death after cardiovascular diseases in western industrialised countries is a complex disease and its etiology and development is still not fully understood. Several hypotheses concerning the mechanisms of carcinogenesis have been discussed in the past. Hanahan and Weinberg suggest that cancer is a multistep process, driven by six essential alterations in cell physiology that dictate malignant growth and that are present in one way or another in all types of cancer: self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of programmed cell death, limitless replicative potential, sustained angiogenesis and tissue invasion and metastasis [5,12].
The last decades of cancer research have brought out a rapidly growing number of mechanism-based therapeutics, that directly target specific molecular structures that are involved in these alterations present in cancer cells.
In this thesis, data on anti-cancer drugs approved via the European Centralised Procedure during the years 1995 to 2009 was derived by a screening of the database for human medicines on the website of the European Medicines Agency. Additionally, detailed data on the mode of action of the identified anti-cancer medicines was received by a review of the European Public Assessment Reports as well as the Summary of Product Characteristics.
A total of 50 anti-cancer drugs were approved in the period of observation including 47 reference medicinal products, two generic approvals and one informed consent approval. 15 anti-cancer medicines got an orphan designation. Among those were four medicines that additionally were approved under exceptional circumstances. Two anti-cancer drugs received a conditional marketing approval. The identified drugs were categorised according to their pharmacotherapeutic class and include alkylating substances, antimetabolites, antimitotics, antibiotics, topoisomerase inhibitors, other cytostatics, hormones, cytokines, immunomodulating substances, antibodies, inhibitors of signal transduction and one drug used in photodynamic therapy.
As the desired effect of these drugs mainly results in the inhibitory activity against one specific target, the responses to this treatment observed in the clinical practice often have been transitory with several relapses of the disease. As a consequence one has to take into account that cancer is a complex disease and that the acquired capabilities of cancer suggested by Hanahan and Weinberg share redundant signalling pathways, meaning that a targeted therapeutic agent inhibiting only one specific key pathway may not completely succeed in the struggle against the tumour cells. This knowledge will be of crucial importance for future cancer research and drug development.

Pages: 66