Cytostatic Agents—Tyrosine Kinase Inhibitors Utilized in the Treatment of Solid Malignancies

Metallothionein isoforms as double agents – Their roles in carcinogenesis, cancer progression and chemoresistance

“…Many TKIs have been developed and approved across a wide range of tumor types to determine the critical roles of tyrosine kinases in regulating cellular signaling and tumor growth in patients (Gillis and McLeod, 2016). Inhibition by this class of cytotoxic agents is mediated through direct competition for ATP binding in the tyrosine kinase domain (genistein, lavendustin, imatinib, erlotinib, gefitinib, sorafenib), allosteric inhibition of tyrosine kinases (lavendustin A), inhibition of ligand binding to receptor tyrosine kinases (ecetuximab), inhibition of tyrosine kinase interaction with other proteins, or destabilization of the tyrosine kinase (herbimycin A and radicicol) (Reeves, 2016). However, acquired resistance of TKIs to targeted therapies inevitably occurs (Camidge et al, 2014).…”

“…MT-1E, MT3 etoposide (Dutta et al, 2002) MT-1E, MT3 vinblastine (Dutta et al, 2002) MT-1E, MT3 paclitaxel (Dutta et al, 2002) MT1-X genistein (Raschke et al, 2006) Gastric cancer MT-1G docetaxel (Pan et al, 2016) MT-1X irinotecan (Chun et al, 2004a) MT-1G cisplatin (Suganuma et al, 2003) NSCLC MT-1H doxorubicin (Mattern and Volm, 1992) Ovarian cancer Total MTs, MT-2A cisplatin (Andrews et al, 1987;Cheng et al, 2006;Surowiak et al, 2005) CRC MT-1G oxaliplatin (Arriaga et al, 2017;Arriaga et al, 2014) Breast cancer MT-1/2 doxorubicin HCC MT-1G, MT-1B, MT-1E, MT-1L, MT-1M sorafenib (Houessinon et al, 2016;Reeves, 2016;Sun et al, 2016) Total MTs carboplatin (Choi et al, 2004;Endo et al, 2004) Lymphoma MT-2A gallium nitrate (Yang and Chitambar, 2008;Yang et al, 2007) Gastrointestinal Stromal Tumor Total MTs imatinib (Perez-Gutierrez et al, 2007) Cardioprotection* Total MTs doxorubicin (Guo et al, 2014;Jing et al, 2011;Sun et al, 2001;Wang and Kang, 1999) *Not a cancer type but another biological functionality described for MTs.…”