For instance, downregulation of receptor surface expression has been indicated in some studies as a mechanism of acquired drug resistance. A reduced expression of CD95 was found to play a role in treatment-resistant leukaemia [62] or neuroblastoma [63] cells. Reduced this website membrane expression of death receptors and abnormal expression of decoy receptors have also been reported to play a role in the evasion of the death signalling pathways

in various cancers [64]. In a study carried out to examine if changes in death ligand and death receptor expression during different stages of cervical carcinogenesis were related to an imbalance between proliferation and apoptosis, Reesink-Peters et al AZD5363 manufacturer MI-503 solubility dmso concluded that the loss of Fas and the dysregulation of FasL, DR4,

DR5, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the cervical intraepithelial neoplasia (CIN)-cervical cancer sequence might be responsible for cervical carcinogenesis [65]. 4. Targeting apoptosis in cancer treatment Like a double-edged sword, every defect or abnormality along the apoptotic pathways may also be an interesting target of cancer treatment. Drugs or treatment strategies that can restore the apoptotic signalling pathways towards normality have the potential to eliminate cancer cells, which depend on these defects to stay alive. Many recent and important discoveries have opened new doors into potential new classes of anticancer drugs. This Section emphasises on new treatment options targeting some of the apoptotic defects mentioned in Section 3. A summary of these drugs and treatment strategies is given in Table 2. Table 2 Summary of treatment strategies targeting apoptosis Treatment strategy Remarks Author/reference Targeting the Bcl-2 family of proteins     Agents that target the Bcl-2 family proteins Oblimersen sodium     Reported to show chemosensitising effects in combined treatment with conventional anticancer drugs in chronic myeloid leukaemia patients and an improvement in survival in these patients Rai

et al., 2008 [66], Abou-Nassar and Brown, 2010 [67]   Histamine H2 receptor Small molecule inhibitors of the Bcl-2 family of proteins     Molecules reported to affect gene or protein expression include sodium butyrate, depsipetide, fenretinide and flavipirodo. Molecules reported to act on the proteins themselves include gossypol, ABT-737, ABT-263, GX15-070 and HA14-1 Kang and Reynold, 2009 [68]   BH3 mimetics     ABT-737 reported to inhibit anti-apoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-W and to exhibit cytotoxicity in lymphoma, small cell lung carcinoma cell line and primary patient-derived cells Oltersdorf et al., 2005 [69]   ATF4, ATF3 and NOXA reported to bind to and inhibit Mcl-1 Albershardt et al.