PolyADP-ribose polymerase (PARP) inhibitors (PARPis) represent the first clinically approved drugs able to provoke “synthetic lethality” in patients with homologous recombination-deficient (HRD) tumors. Four PARPis have just received approval for the treatment of several types of cancer. Besides, another three additional PARPis underlying the same mechanism of action are currently under investigation. Despite the success of these targeted agents, the increasing use of PARPis in clinical practice for the treatment of different tumors raised the issue of PARPis resistance, and the consequent disease relapse and dismal prognosis for patients. Several mechanisms of resistance have been investigated, and ongoing studies are currently focusing on strategies to address this challenge and overcome PARPis resistance. This review aims to analyze the mechanisms underlying PARPis resistance known today and discuss potential therapeutic strategies to overcome these processes of resistance in the future.

Primary malignant cardiac tumors are rare, with a prevalence of about 0.01% among all cancer histotypes. At least 60% of them are primary soft tissue sarcomas of the heart (pSTS-h) that represent almost 1% of all STSs. The cardiac site of origin is the best way to classify pSTS-h as it is directly linked to the surgical approach for cancer removal. Indeed, histological differentiation should integrate the classification to provide insights into prognosis and survival expectancy of the patients. The prognosis of pSTS-h is severe and mostly influenced by the primary localization of the tumor, the difficulty in achieving complete surgical and pharmacological eradication, and the aggressive biological features of malignant cells. This review aims to provide a detailed literature overview of the most relevant issues on primary soft tissue sarcoma of the heart and highlight potential diagnostic and therapeutic future perspectives.