For instance, human caspase-3 gene therapy was used in addition to etoposide treatment in an AH130 liver tumour model and was found to induce extensive apoptosis and reduce tumour volume [102] while gene transfer of constitutively active caspse-3 into HuH7 human hepatoma

cells selectively induced apoptosis in these cells [103]. Also, a recombinant adenovirus carrying immunocaspase 3 has been shown to exert anti-cancer effects in hepatocellular carcinoma in vitro and in vivo [104]. 4.5 Molecules targeting apoptosis in clinical trials Recently, many new molecules that target apoptosis enter various stages of clinical trials. A search at http://​www.​clinicaltrials.​gov (a registry and results Y-27632 ic50 database of federally and privately supported clinical trials conducted in the United States and around the world) returns many results. These molecules target Epigenetics inhibitor various proteins involved in apoptosis. Many are antagonists of IAPs and molecules that target the Bcl-2 family of mTOR phosphorylation proteins. Table

3 summarises ongoing or recently completed clinical trials involving molecules that target apoptosis. Table 3 Ongoing or recently completed clinical trials involving molecules that target apoptosis Molecule name Sponsor Target Condition Clinical stage ABT-263 (in combination with erlotinib or irinotecan) Abbott Bcl-2 family of proteins Solid tumours Phase I ABT-263 (in combination with docetaxel) Abbott Bcl-2 family of proteins Solid tumours Phase I ABT-263 (in combination with paclitaxel) Abbott Bcl-2 family of proteins Chronic lymphocytic leukaemia Phase I ABT-263 Genentech Bcl-2 family of proteins Chronic lymphocytic leukaemia Phase II AT-101 (Gossypol) Roswell Park Cancer Institute Bcl-2 family of proteins Lymphocytic leukaemia, chronic B-cell leukaemia Phase I Phase II AT-406 Ascenta Carbohydrate Therapeutics IAPs Solid tumours, lymphoma Phase I AT-406 Ascenta Therapeutics IAPs Acute myelogenous leukaemia Phase I ENZ-3042 Therapeutic Advances in Childhood Leukaemia Consortium IAPs Acute, childhood and T cell lymphoblastic leukaemia Phase I GX15-070MS (Obotoclax)

Children’s Oncology Group Bcl-2 family of proteins Leukaemia, lymphoma unspecified childhood solid tumour Phase I GX15-070MS (Obotoclax) Arthur G. James Cancer Hospital & Richard J. Solove Research Institute Bcl-2 family of proteins Lymphoma Phase I Phase II HGS-1029 Human Genome Sciences IAPs Advanced solid tumours Phase I HGS-1029 Human Genome Sciences IAPs Advanced solid tumours Phase I LCL-161 Novartis Pharmaceuticals IAPs Solid tumours Phase I RO5458640 Hoffmann-La Roche TNF-like weak inducer of apoptosis (TWEAK) ligand Advanced solid tumours Phase I 5. Conclusions The abundance of literature suggests that defects along apoptotic pathways play a crucial role in carcinogenesis and that many new treatment strategies targeting apoptosis are feasible and may be used in the treatment of various types of cancer.