Targeting iron addiction: Mechanism of action of salinomycin and its synthetic derivative ironomycin against persister cancer cells. This involves lysosomal iron targeting, production of reactive oxygen species (ROS) and cell death by ferroptosis.
A deeper picture of cancer biology Every individual case of cancer is different, and the chromatin structure inside a cell plays a major role in determining how patients respond to treatment. We spoke to Dr Raphael Rodriguez about his research into how patients respond to anti-cancer drugs, which could lay down the foundations for more personalised treatment in future.
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The effectiveness of cancer treatment
Gene expression
can vary according to the physiology and genetic background of each individual patient, a topic of great interest to researchers. Based at the Institut Curie in Paris, Dr Raphael Rodriguez is a Research Director at the CNRS, a role in which he is probing deeper into cancer biology. “One of the major aims in our research is to better understand the molecular features of each patient, starting from their genetic and epigenetic features,” he outlines. The structure of chromatin, a component of eukaryotic cells, which is comprised of DNA and proteins, is an important consideration in that respect. “The DNA sequence is a major factor in the structure of chromatin,” explains Dr Rodriguez. “A second point is the histones, proteins around which DNA is wrapped. These histones can be chemically modified, and it is these modifications that essentially determine how the DNA is packed and whether it is accessible to other proteins.”
This helps to determine which genes are expressed or repressed and the defects that may be present in a cell, important considerations in terms of Dr Rodriguez’s wider research agenda. Some existing anticancer drugs target proteins that interact with DNA, or proteins that interact with chromatin, and the effectiveness of these approaches will depend to a degree on how chromatin is structured. “The response of individual patients will be different. This is what we are trying to understand,” says Dr Rodriguez. Cancer is often very heterogeneous in terms of cell types however, which adds another layer of complexity to Dr Rodriguez’s research. “We know that using one drug for a patient doesn’t work, because there are different types of cells and different types of defects,” he continues. “What we can do is try to identify the different types of cells and treat them with a combination of drugs.”
A major challenge here is to understand the heterogeneity of a particular cancer, which could then inform clinical decisionmaking and lead to improved outcomes for patients. Researchers in Dr Rodriguez’s group are using DNA sequencing to identify an individual’s genetic and epigenetic features, which will help clinicians choose the most effective drug for that particular patient. “That’s one aspect of what we are trying to achieve,” he explains. This research also holds relevance to understanding cancer resistance; for many years researchers struggled to identify the different types of cells in cancer, failing to recognise that some of the cells in a tumour do not divide as quickly as others. “That’s quite a natural thing to do in a way. When you use an antiproliferative drug and see that the tumour is shrinking then that’s a positive outcome,” points out Dr Rodriguez. “What you do not know is whether the remaining cells are dividing aggressively, and what’s going to happen when you stop this treatment.”
EU Research
