Cancer is considered the second leading cause of death worldwide. In 2012, about 14.1 million new cancer cases and 8.2 million cancer-related deaths were registered, while in 2015, the number of deaths increased to over 8.7 million.
Chemotherapy is one of the main cancer treatments that uses anticancer drugs in a standardized treatment regimen. Platinum-based drugs (DNA-damaging molecules) are among the most effective anticancer therapies, and cisplatin is the most widely-used drug in this family of DNA-damaging molecules.
Cisplatin is a platinum-based drug that inhibits DNA synthesis, and consequently, the growth of tumor cells. Although it is used to treat several human cancers, cisplatin-based chemotherapy is associated with serious side effects, such as neurotoxicity and muscle wasting, resulting in a significant body weight loss.
Clinical data show that the preservation of body weight may increase the chances of survival of cancer patients and improve their quality of life.
Portuguese investigators reviewed the molecular mechanisms involved in chemotherapy-related muscle wasting, as well as the current efforts to preserve muscle mass and quality life among cancer patients. They found that cisplatin is involved in:
Degradation of muscle protein (muscle proteolysis and activation of catabolic pathways)
Inhibition of protein synthesis (inhibition of anabolic pathways)
Increasing the expression of molecules that promote inflammation (pro-inflammatory cytokines)
Based on these molecular mechanisms, the investigators recorded some potential therapeutic strategies to counteract chemotherapy-related muscle wasting, such as:
Ghrelin ( a hormone that induces appetite)
Clarithromycin (an antibiotic with anti-inflammatory properties)
Thalidomide (a drug that attenuates weight loss, possibly by reducing the expression of pro-inflammatory cytokines)
Lastly, Alexandra Pais and the remaining researchers highlight that “Future research should address the contribution of chemotherapeutic agents for the development and exacerbation of muscle wasting, dissecting the molecular pathways responsible for this condition and identifying the most promising therapeutic targets for clinical intervention”.
References:
Moreira-Pais, A., Ferreeira, R., da Costa, R.G. (2018). Platinum-induced muscle wasting in cancer chemotherapy: Mechanisms and potential targets for the therapeutic intervention. Life Sciences, 1-9. DOI: 10.1016/j.lfs.2018.07.010.
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