Wspólnotowy Serwis Informacyjny Badan i Rozwoju - CORDIS

Mechanism of tumour sensitivity to novel DNA damaging drugs

We have developed a novel series of DNA reactive peptides (DR peptides) that carry groups which alkylate DNA and as such resemble conventional alkylating agents i.e. Melphalan.

Our lead DR peptides do, however, circumvent resistance to conventional alkylating agents and in this work we have explored mechanisms behind the efficacy of DR peptides in tumour cell lines.

Moreover, we have studied which combinations of DR peptides and chemotherapy agents that have synergistic effects when used in combination.

In addition, a candidate drug is now underway to formal pre-IND testing. Results show that DR peptides have improved efficiency compared to the lead substance Melfalan in several human tumours cell lines including lines derived from lung cancer.

A synergistic effect between DR peptides and DNA damaging therapy e.g., topo II inhibitors, cyclophosphamide and carboplatin in childhood tumour neuroblastoma.

Our data show that lysosomes are involved in DR peptide induced cell death in tumour cell lines as are stress activated protein kinases. Potential users of this knowledge are pharmaceutical industries developing DNA damaging sensitizing drugs and researchers, which analyze chemoresistance mechanisms.

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Reported by

Cancer Center Karolinska, Karolinska Institutet
CCK, Karolinska University Hospital, R8:00
17677 Stockholm
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