Cancer is quoted as one of the world's leading causes of death, accounting for approximately 14 million new cases and around 8 million deaths worldwide in 2012.
According to the World Health Organization (WHO), the burden of cancer on the human society will be even increasing to over 20 million new cases worldwide each year by 2025, mainly due to population growth and ageing. Regarding these appalling numbers, cancer can be considered as key public health concern and threat to healthcare services.
For decades, the use of platinum-based drugs is one of the most important strategies in the daily clinical routine. Treating a broad range of tumor types, cisplatin, carboplatin and oxaliplatin are involved in almost every 2nd chemotherapeutic regime.
Very recent clinical studies revealed that immune checkpoint inhibitors, when combined with platinum drugs, are highly superior compared to immunotherapy alone. This chemo-immunotherapy combination is likely to be the future first-line treatment for various cancer types meaning that platinum-based therapeutics will keep their prominent position in the clinic.
However, besides drug resistance especially the occurrence of adverse effects and the short plasma half-life of the applied (small-molecular) drugs are the major limitations for successful anticancer therapy. This is also reflected by the fact that only about 1 % of the administered platinum dose reaches the target inside the cancer cell. In addition, high amounts of the drug are accumulating in healthy tissue resulting in considerable (dose-limiting) side effects (e.g. nephro- and neurotoxicity, ototoxicity) that highly affect the patient's quality of life and result in treatment termination.
Nevertheless, the effectiveness of platinum complexes in the fight against cancer is undeniable and in the light of the striking synergism with immunotherapy, the optimization of those compounds towards enhanced tumor specificity and tolerability is urgently needed.
With Albuplatin we will develop the next generation of platinum drugs to overcome these drawbacks. Albuplatin is a non-toxic double prodrug that carries an inactivated drug core. With an innovative two-step strategy, in which Albuplatin binds to the plasma protein albumin, the initially inactive substance is tumor-specifically accumulated. By binding to albumin, Albuplatin is being infiltrated undetected like a „Trojan horse“ in the tumor cells and is being released as a result of the albumin degradation. Finally, Albuplatin is activated by reduction in the tumor cells, generating the active species which can kill the cancer cells. These unique, innovative properties make Albuplatin a promising candidate to represent the next generation of platinum-based therapy.
Intravenous injection of Albuplatin
Albuplatin rapidly binds to the plasma
Selective accumulation in the tumor tissue
Albumin-Albuplatin conjugate enters the
cancer cell like a Trojan Horse
Activation of Albuplatin inside the tumor cell
Induction of apoptotic cell death
MODE OF ACTION
DR. NADINE S.
UNIV-PROF. DR. DR.
BERNHARD K. KEPPLER