Compounds from a Brazilian tree bark can now be used to treat acute myeloid leukaemia after a new technique that delivers it straight into the cancer cell.
The disease has a survival rate of around 20% after five years, and there is a high occurrence of relapse.
Caused by an abnormal increase in the number a type of immature blood cells, it is an aggressive cancer and the most common form of acute leukaemia in adults.
Scientists identified a compound from the bark of the lapacho tree called β-lapachone which controls the increase in the number of cells involved with cancer, however it was toxic to other cells as well.
“It’s important to find new therapeutic strategies for acute myeloid leukemia,” Professor Gonçalo Bernardes, a reader in Chemical Biology and a Royal Society University Research Fellow and a Fellow of Trinity Hall College, Cambridge said. “There are a lot of natural compounds with medicinal value that can’t be used as therapies at the moment due to toxicity and negative effects in healthy cells.
“In our work, we used these natural compounds and modified them in a way that controls their negative effects and allows us to take advantage of their therapeutic value.”
The team modified the compound to shield the body from its negative effects until it is delivered to the heart of the cancer cell.
“The compound that we explored in this study, called β-lapachone, is a promising drug to treat leukaemia, but its reactive properties could have undesirable effects,” Prof Bernardes who is also group leader at the Instituto de Medicina Molecular (iMM) and co-leader of the study added.
“In this work, we combined two strategies to minimise the negative effects of the compound.
“On one side, we added a chemical group to this compound that protects from its reactive properties. It acts like a mask that covers the toxicity of the drug.
“This mask is released in a more acidic environment, that corresponds to the interior of cells.
“This leads to our second strategy. We attached the modified compound to a protein, an antibody, that delivers it directly to the interior of cancer cells.”
The chemistry that was developed in this study, published in the journal Nature Chemistry, can be used for other valuable natural compounds, enabling the use of compounds with therapeutic potential that were previously inappropriate for medicinal use.
“Cancer cells have certain marks that tell them apart from healthy cells,” Dr Ana Guerreiro, co-second author of the study, added. “In acute myeloid leukaemia we know that one of these specific markers, called CD33, is present in the cancer cells.
“We attached our natural product to an antibody that binds specifically to this CD33.
“This allows the drug to go through the body without damaging any healthy cells and when the antibody encounters the cancer cell, it binds to the CD33 marker and delivers the drug.
“At this moment it will turn into its active and toxic form, killing the cancer cell.”