Differential Role of HDAC in Cancer Cachexia

Cachexia frequently develops in advanced stages of various chronic diseases such as chronic heart failure, chronic obstructive pulmonary disease, end-stage renal disease, sepsis, acquired immune deficiency syndrome and numerous kinds of cancer.
Cancer patients exhibit severe weight loss due to skeletal muscle wasting and loss of adipose tissue. Due to which they are less tolerable to chemotherapy, having more side effects and poor quality of life. The patients have an altered body image, which impacts their emotions, spirituality, relationships and social functioning. Lives are restricted and isolated, which is compounded by emotional distancing bycare-givers and health care professionals. Hence, addressing the issue of cachexia is the need of the hour.
Dr Bhoomika M Patel from Institute of Pharmacy, Nirma University, undertook this issue and received a major research grant for “Exploring the effect of Histone Deacetylases (HDAC) in cancer-cachexia and their downstream targets” from Science, Engineering and Research Board (SERB), Government of India.
Using animal models of cachexia, our findings have shown that Class I Histone Deacetylases (HDAC) inhibitor produces beneficial role in cancer cachexia and associated cardiovascular complications while Class II HDAC inhibitor produces the detrimental effect. Non-specific HDAC inhibitor sodium butyrate produces partial beneficial role in cancer cachexia but produced no improvement in cardiovascular complication associated with cancer cachexia.
This extensive study provides and important outcome that Class I and Class II HDACs exhibit differential effect in cancer cachexia. Thus, it is now a point of concern that the novel anti-cancer agents (acting through HDAC inhibition) which are under investigation and also those which are already marketed are beneficial or harmful with respect to cachexia.