Muscular dystrophies share pathogenetic mechanisms with muscle sarcomas

• We reviewed the mouse models of muscular dystrophy developing rhabdomyosarcoma.
• Aging and the disrupted muscle niche provide the basis of cancer susceptibility.
• Oxidative stress in dystrophic, aged muscle favors the accumulation of DNA damage.
• DNA damage predisposes to cancer in the regenerating, fibrotic, and inflamed dystrophic muscle.

Several lines of recent evidence have opened a new debate on the mechanisms underlying the genesis of rhabdomyosarcoma, a pediatric soft tissue tumor with a widespread expression of muscle-specific markers. In particular, it is increasingly evident that the loss of skeletal muscle integrity observed in some mouse models of muscular dystrophy can favor rhabdomyosarcoma formation. This is especially true in old age. Here, we review these experimental findings and focus on the main molecular and cellular events that can dictate the tumorigenic process in dystrophic muscle, such as the loss of structural or regulatory proteins with tumor suppressor activity, the impaired DNA damage response due to oxidative stress, the chronic inflammation and the conflicting signals arising within the degenerated muscle niche.