Physical Activity and Sarcoma, Role and Impact on Outcome

The protective role of physical activity (PA) has been demonstrated in numerous diseases, especially cardiovascular and metabolic ones, but also in various neoplastic pathologies.

It has been estimated that approximately 25% of cancer cases globally are due to excess weight and a sedentary lifestyle. Regular moderate-intensity or greater physical activity is associated with a reduced risk of several types of cancer. Most studies have shown this association especially for breast, colon, and endometrial cancer.

The mechanisms through which PA may decrease cancer risk are numerous: physical activity might work through reducing the amount of adipose tissue, thereby lowering circulating levels of estrogens and other sex hormones, PA improves insulin resistance, reduces hyperinsulinaemia, might reduce inflammatory markers, thereby decreasing the exposure to these potentially carcinogenic hormones and peptides, reduces oxidative stress, reduces gastrointestinal transit time and improves immune system by increasing the phagocytic activity of macrophages and neutrophils, and increasing the proliferation of natural killer cells and lymphocytes. Other mechanisms under investigation pertain angiogenesis, DNA repair, and growth factors.

In addition to hormone-sensitive tumors and colon cancer, new evidence suggests that similar associations with PA might exist for other cancers for which less is known about the potential mechanisms underlying the physical activity association, suggesting that further mechanistic research is warranted.

Furthermore, in people who have already been diagnosed with cancer and are undergoing oncological therapy, regular exercise helps to counteract some typical and common side effects of anti-cancer therapies, thus improving treatment compliance and the overall quality of life. In particular, physical activity seems to reduce fatigue, arthralgia, nausea, improves cardiovascular and respiratory capacity, reduces the risk of osteoporosis, and anxiety.

Even more, several studies have shown that in patients already affected by cancer, physical activity could be associated with a better prognosis, reducing risk of recurrence and increasing survival. The most important and largest studies are mainly aimed at breast, colorectal, prostate and ovarian cancer \[5-8\].

Due to their rarity and extreme histological-molecular heterogeneity, little is known about sarcomas, particularly regarding potential risk factors and possible factors that may influence their clinical course.

Furthermore, starting from the evidence that cardiac tumors, both primary and secondary, are extremely rare, the possible mechanisms responsible for this favorable "refractoriness" of myocardial cells to neoplastic transformation and/or to the engraftment of other neoplastic cells will be studied.

The property of cardiomyocytes most likely related to this phenomenon is their contractility and continuous exposure to mechanical load that halt cardiomyocyte proliferation in the human heart. This project aims at improving knowledge about the molecular landscape and genetic aberrations involved in pathogenesis of cardiac tumors and assessing whether the mechanical forces generated by cardiomyocyte contraction in a beating heart inhibit the proliferation of cancer cells, thus protecting the heart from cancer.

Engineered heart tissue will be used to silence candidate mechanosensing genes. This should make the cell unresponsive to mechanical stimulation and thus allow it to proliferate even with increased afterload.

The expression levels of the mechanosensing genes eventually identified, will be tested in tumor tissue from sarcoma as located in the extremities of physically active individuals to assess whether they are downregulated, thus making the cells able to proliferate although located in actively contracting skeletal muscles.

Confirmation of the role of physical activity on cancer is awaited with interest. Understanding the mechanisms that link physical activity with cancer will be useful for several reasons. First, the identification of this mechanisms can give new clues to cancer biology, which might help in designing other cancer prevention and innovative treatment modalities. Second, if further data accumulate showing that increased physical activity can prevent some cancers or improve outcomes, this would constitute an excellent public health intervention to reduce the impact of cancer risks and costs.