Last month, we covered some of the most recent advances in cancer therapy (Mendes, 2020). However, a significant issue worthy of discussion relates to the adverse effects of cancer treatments. Research into developing therapies to target cancer cells without causing damage to other cells is ongoing, and comorbidities resulting from treatment are an important concern for long-term cancer survivors.
Cardiotoxicity
Cardiomyopathy or cardiac damage resulting from chemotherapy, radiation and anti-cancer signalling inhibitors is a major consideration (Myatt, 2015). Increases in life expectancy following anti-cancer therapy are countered by increased mortality from cardiac conditions, such as heart failure, myocardial infarction, arrhythmias, hypertension and thromboembolism (Bovelli et al, 2010). For example, quite alarmingly, in long-term survivors of Hodgkin's disease, myocardial infarction accounts for 25% of deaths (Curigliano et al, 2012).
Although chemotherapy is a highly effective cancer therapy, high doses can result in heart failure, which can be both debilitating and life-threatening (British Heart Foundation (BHF), 2020). To prevent this, cancer specialists often prescribe chemotherapy agents in lower doses, which are less effective at destroying cancer cells (BHF, 2020). There are approximately 50 chemotherapeutic agents; of these, the most commonly used is doxorubicin (BHF, 2020). According to the BHF (2020), among the small number of people who receive the maximum dose of doxorubicin, 7% will develop heart failure. Therefore, research is needed into potential ways to prevent the cardiotoxic effects of doxorubicin and other cardiotoxic cancer therapies (Suter and Ewer, 2013).
Current research
The drug doxorubicin slows or stops the spread of cancer cells by blocking the enzyme topoisomerase, which cancer cells rely on for division and growth (Cancer Research UK (CRUK), 2019). It is used to treat various types of cancer, such as those of the bladder and breast, as well as non-Hodgkin's lymphoma, Hodgkin's disease and acute lymphatic leukaemia. It can result in cardiac dysfunction and heart failure (Suter and Ewer, 2013).
A recent study published in Nature Cancer reported the identification and use of the experimental drug BAI1 to prevent doxorubicin-induced cardiomyopathy in mice—without interfering with its ability to kill cancer cells (Amgalan et al, 2020). The researchers discovered that a protein called BAX initiates apoptosis and necrosis, leading to the death of heart cells; BAI1 binds to BAX and blocks both of these biological processes (National Cancer Institute (NCI), 2020). Amgalan et al (2020) showed that, in mouse models of breast cancer and leukaemia, treatment with doxorubicin, as well as BAI1, shrank tumours without causing any damage to the heart, while treatment with doxorubicin alone shrank tumours, but led to heart damage (NCI, 2020).
Looking ahead
A clinical trial is being planned to test the use of BAI1 or perhaps an analog to inhibit BAX in patients receiving doxorubicin (NCI, 2020). Other research investigating how to protect against cardiac damage from anthracycline drugs including doxorubicin and epirubucin is also under way (CRUK, 2020).