Moana Tercel

University of Auckland

Moana is an Auckland graduate who won a Rutherford Scholarship to pursue her PhD study in synthetic organic chemistry at the University of Cambridge. Here she worked on the total synthesis of the plant alkaloid gelsemine, under the supervision of Dr Ian Fleming. She then spent two years as an Alexander von Humboldt Research Fellow at the Max Planck Institute for Medical Research in Heidelberg, before returning to New Zealand in 1991 to take up a position in anticancer drug development at the Auckland Cancer Society Research Centre.  She is currently a Senior Research Fellow in this centre and an Associate Investigator of the Maurice Wilkins Centre. Moana's present research interests are in hypoxia-activated prodrugs, DNA alkylating agents, nitroimidazole biomarkers of hypoxia, and antibody-drug conjugates.

Converting toxic duocarmycin natural products to tumour-selective anticancer agents

Duocarmycins are a rare class of bacterial natural products with exceptional cytotoxic potency and a unique mechanism of action involving DNA alkylation. Synthetic and semisynthetic analogues have promising preclinical antitumour activity, but toxicity in clinical trials has prevented further development. This talk will discuss two alternative strategies to add a tumour-selective delivery or activation mechanism to duocarmycin analogues. The first involves using duocarmycin analogues as payloads for antibody-drug conjugates, where extreme cytotoxicity is a necessary attribute; while the second involves converting duocarmycins to hypoxia-activated prodrugs, where DNA-alkylating ability is only activated under low-oxygen conditions as commonly found in tumours.