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The impact of P-glycoprotein and MRP expression on SCLC response Between 1970 and 1994, 2.5 million Americans died from lung cancer, a disease grouping that includes small cell (SCLC) and non-small cell lung cancers. As well as being one of the most common forms of cancer, affecting 57 out of every 100,000 people (1990-1991 data), this class of cancer is characterized by a very poor 5-year survival rate. Without treatment, SCLC has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. New treatment are therefore required. Compared with other types of lung cancer, SCLC has a greater tendency to be widely disseminated by the time of diagnosis, but is much more responsive to chemotherapy and irradiation. However SCLC frequently develops resistance to chemotherapies. Expression of the (MDR1) gene, which encodes P-glycoprotein and the multidrug resistance 1-related protein (MRP) gene, both of which are associated with the development of drug resistance, is very common in SCLC. Chinese researchers have now evaluated retrospectively the relationship between chemotherapy responses of SCLC patients and the expression of MDR1and MRP. Of 23 SCLC patients with poor response to chemotherapy, 11 had positive P-glycoprotein and MRP expressions, 2 had positive P-glycoprotein but negative MRP expressions, 6 had positive MRP but negative P-glycoprotein expressions, and 4 patients had negative P-glycoprotein and MRP expressions. All 27 SCLC patients with good response had negative P-glycoprotein and MRP expression. A considerable level of research has been conducted over past years to establish a therapeutic benefit for the use of inhibitors that target multidrug resistance proteins. Consequently around 20 such molecules are in preclinical or clinical development. This study further highlights the therapeutic benefit of these molecules and suggests that for full therapeutic activity non-specific inhibitors may be required. Entry date October, 2002 Adapted from Hsia et al, Lung 2002;180(3):173-9
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