Written by Charlotte Harrison, Science Writer
Cancer survivors have an increased risk of cardiovascular diseases, which is thought to stem from their prior use of anticancer therapies. Nearly all cancer therapeutics, including chemotherapies, immune checkpoint inhibitors and monoclonal antibodies, are associated with cardiovascular complications.
A new review, published in Cell & Bioscience advocates for more research into cardio-oncology. Cardio-oncology investigates the molecular mechanisms by which anticancer treatments lead to cardiovascular dysfunction and investigates novel strategies to counteract the cardiotoxic effects of cancer therapies.
The review highlights how non-coding ncRNAs (ncRNAs) — which can be divided into long non-coding RNAs (lncRNA) and microRNAs — are at the heart of the link between anti-cancer drugs and cardiovascular complications. Importantly, ncRNAs could be new biomarkers of cancer drug-induced cardiotoxicity or therapeutic targets to combat cardiotoxicity.
The long of it: lncRNAs
LncRNAs play an essential role in the progression of cancer and cardiovascular disorders. This is achieved through various alterations in the expression of genes and proteins involved in numerous cellular signalling pathways. One important mechanism by which LncRNAs are involved in the pathology of cancer and cardiovascular disease involves mitochondrial dysfunction. Some lncRNAs protect against cancer therapy-induced cardiotoxicity, and some lncRNAs are associated with an increased risk of cancer therapy-induced cardiotoxicity.
Although lncRNAs are found ubiquitously within the pathology of cancer and cardiovascular disease, relatively little is known about them.
And the short of it: microRNAs
In cancers, miRNAs can be either oncogenic or tumour suppressors. Oncogenic miRNAs target and downregulate tumour suppressors, resulting in cell proliferation and an enhanced strength of the tumour. Other microRNAs interfere with proteins present in the cell to suppress oncogenic activity. Like lncRNAs, some microRNAs protect against cancer therapy-induced cardiotoxicity, and some lncRNAs are associated with an increased risk of cancer therapy-induced cardiotoxicity.
Cancer treatments are known to modulate microRNA levels, and the differential expression of certain microRNAs may affect the occurrence of cardiotoxicity.
What are the priorities in cardio-oncology?
The review has several suggestions to propel the field of cardio-oncology forward:
- Research should focus on the mode of action of anticancer drugs in both cancerous and cardiac cell types.
- ncRNAs in the circulation present an opportunity for novel diagnostic and prognostic markers of cardiovascular disease; large clinical studies are needed.
- Further studies are needed to determine if lncRNAs can act as a diagnostic tool to predict anticancer therapy-induced cardiotoxicity.
- Differentially regulated ncRNAs, especially lncRNAs, could be new therapeutic targets to counteract the cardiotoxicity of anticancer drugs; this will need to be achieved without altering the effects of anticancer drugs or disease progression.
- Better animal models are needed, including an in-vivo humanized animal model that can be used to study non-conserved human lncRNAs specific to the heart.
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