Overcoming resistance in anticancer therapy
EC-funded IMPALED project set out to develop new anticancer regimens, concentrating on treatment resistant tumours. The main emphasis was placed on the interplay between mitochondria and the p53 family of proteins. It is the p53 proteins, which sense DNA damage and can lead to apoptotic pathways. Project partner, Karolinska Institute, developed a series of compounds aimed at enhancing the sensitivity of tumour cells to anticancer drugs. These DNA reactive peptides (DR peptides) act in a similar way to a group of known anticancer agents, the alkylating agents. However, unlike the common alkylating agents, the DR peptides can overcome common treatment resistance mechanisms in tumour cells. Studies showed that DR peptides fare better compared to conventional alkylating agents such as melphalan. Furthermore, synergistic effects between DR peptides and DNA damaging drugs were evident in certain studies. Pharmaceutical companies could explore these findings further and evaluate the commercial impact of these discoveries.
