Matrix metalloproteinase and its drug targets therapy in solid and hematological malignancies: an overview.
Matrix metalloproteinase (MMP) comprises a family of zinc-dependent endopeptidases that degrade various components of the extracellular matrix (ECM) and basement membrane. MMPs are involved in solid and hematological malignancy through modification of cell growth, activation of cancer cells and modulation of immune functions. Several polymorphisms of different MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A) & MMP-9 (-1562 C/T) and their expression levels have been well documented in different types of solid cancer. These polymorphic variations were found to be associated with angiogenesis, cancer progression, invasion and metastasis. There is paucity of data available in the field of hematological malignancies. Hence the field of matrix biology of hematological malignancies is an area of active exploration. A number of MMP inhibitors (MMPIs) have been developed for the cancer treatment. The most extensively studied classes of MMP inhibitors include Batimastat, Marismastat, Salimatat, Prinomastat and Tanomastat. However, their efficacy and action have not been confirmed and more data is required. The application of one or more selective targeted MMPIs in combination with conventional anti-leukemic treatment may represent a positive approach in combat against hematopoietic malignancies. Balance of MMPs and TIMPs is altered in different malignancies and biochemical pathways. These alternations will add another dimension in the matrix biology of both solid tumor and leukemia. MMP and TIMP singly and in combination are increasingly being recognized as an important player in basic cellular biology. Exploration and exploitation of MMP and TIMP balance in various malignant and nonmalignant lesions is going to be one of the most interesting facets of future use of this system for human health care.
Department of Haematogenetics, National Institute of Immunohaematology (NIIH), Indian Council of Medical Research (ICMR), King Edward Memorial (KEM) Hospital Campus, 13th Floor, NMS Bldg., Parel, Mumbai 400 012, India. Electronic address: ajaygenome@gmail.com.
Ajay Kumar
AK
Chaudhary
Haematopathology Lab, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai 400 012, India. Electronic address: shrutigentech@gmail.com.
Shruti
S
Pandya
Department of Haematogenetics, National Institute of Immunohaematology (NIIH), Indian Council of Medical Research (ICMR), King Edward Memorial (KEM) Hospital Campus, 13th Floor, NMS Bldg., Parel, Mumbai 400 012, India. Electronic address: kanjakshaghosh@hotmail.com.
Kanjaksha
K
Ghosh
Department of Haematogenetics, National Institute of Immunohaematology (NIIH), Indian Council of Medical Research (ICMR), King Edward Memorial (KEM) Hospital Campus, 13th Floor, NMS Bldg., Parel, Mumbai 400 012, India. Electronic address: anitahnadkarni@yahoo.com.
Anita
A
Nadkarni
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use*; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases
Drug targets therapy; Hematological malignancies; MMPs; Polymorphism and solid cancer; SNPs