DNA Repair: Cancers and Diseases

**143**

**Chapter 7**

**Abstract**

with sarcomas.

**1. Introduction**

DNA Repair Defects in Sarcomas

DNA repair pathway is considered to be one of the most important mechanisms that protect cells from intrinsic and extrinsic stresses. It has been established that DNA repair activity has a crucial role in the way that cancer cells respond to treatment. Sarcomas are a group of tumors with mesenchymal origin in which their association with DNA repair aberrations has been reported in numerous studies. Special attention has been focused on exploiting these alterations to improve the patient's overall survival and overcome drug resistance in cancer. While there is a large degree of heterogeneity among different types of sarcomas, DNA repair alteration is found to be a common defect in the majority of patients. In this chapter, we will introduce and review some of the most important dysregulated components involved in the DNA repair system, and discuss their association with tumorigenesis, cancer aggressiveness, drug resistance, and overall prognosis in the patients

*Niknam Riyahi, M. Reza Saadatzadeh,* 

*Pankita H. Pandya and Karen E. Pollok*

*Khadijeh Bijangi-Vishehsaraei, Farinaz Barghi,* 

**Keywords:** DNA repair, Sarcoma, drug resistance, gene alteration

Sarcomas represent a divergent and heterogeneous group of malignancies comprising more than 70 subtypes, with a common characteristic of being derived from mesenchymal lineages such as bone, muscle, cartilage, and fat [1]. Sarcomas are rare, accounting for less than 1% of adult cancers and approximately 15% of childhood malignancies [2]. They occur in all ages with an extensive intertumoral and intratumoral biological heterogeneity and widely varied clinical prognosis [3]. The primary standard of care approach for treatment of sarcoma patients is consist of surgery, radiation, and chemotherapy-based strategies [4]. Although the cure rate for the patients with localized sarcoma is generally more than 70%, the survival rate of metastatic and relapsed patients is still less than 30% and has not been changed in the last decades [1, 2, 5, 6]. Based on the tissue type of primary manifestation, sarcoma tumors could be categorized into two main groups: soft-tissue sarcomas (STS) and bone sarcomas. STS are more common with the incidence of approximately 13,000 reported cases versus 3000 cases of bone sarcomas each year in the United States [4]. Among STS, liposarcoma, leiomyosarcomas, and undifferentiated pleomorphic sarcomas are the most common types in adults, whereas rhabdomyosarcoma is the most common type
