What is INI1 and SMARCA4?

What is INI1 and SMARCA4?

INI1 and SMARCA4 are subunits of SWI/SNF, a chromatin modifying protein complex, which opposes the activity of PRC2, the complex within which EZH2 resides. Loss of INI1 or SMARCA4 in specific cell backgrounds is believed to cause dysregulation in the balance between SWI/SNF and PRC2, and thus cause tumors to become sensitive to EZH2 inhibition. This effect was observed in a preclinical study of tazemetostat in a xenograft model of MRT in which tazemetostat caused a dose dependent regression in INI1-negative tumors. INI1-negative tumors can appear in many different tissue types, and can present as epithelioid sarcoma, MRT, extraskeletal myxoid chondrosarcoma, peripheral nerve sheath tumor, myoepithelial carcinoma and renal medullary carcinoma, among several others. SMARCA4-negative tumors can also appear as different tumor types, including MRTO.
INI1-negative or certain SMARCA4-negative tumors are typically aggressive cancers with few to no approved treatments. For example, current treatment of MRT consists of surgery, chemotherapy and radiation therapy, which are associated with limited efficacy and significant treatment-related morbidity in this population. INI1-negative tumors are most commonly seen in infants through young adults, while SMARCA4-negative tumors are most commonly seen in teenagers and young adults. We believe that approximately 2,000 new patients with INI1-negative tumors and certain SMARCA4-negative tumors are diagnosed annually in the United States and other major pharmaceutical markets; however, we believe that the actual number may be higher, as these types of molecularly defined cancers are significantly under-reported today. MRTO accounts for less than 1% of all ovarian cancer diagnoses, with an average age of 24 years at diagnosis. MRTO is characterized by an aggressive clinical course with a two-year survival rate of less than 35%.

What is a monoclonal antibody?

A monoclonal antibody or mAb is an antibody produced in the laboratory from a single ancestral plasma cell

What Is Non-Hodgkin Lymphoma?

Non-Hodgkin lymphoma (also known as non-Hodgkin’s lymphoma or NHL) is a cancer of the lymphocytes, a type of white blood cells and an important part of the immune system.

What is INI1 and SMARCA4?

INI1 and SMARCA4 are subunits of SWI/SNF, a chromatin modifying protein complex, which opposes the activity of PRC2, the complex within which EZH2 resides.