Oncogene
-
Alemtuzumab (Campath-1H) is a humanized IgG1 monoclonal antibody that targets the human CD52 antigen. CD52 is expressed by a variety of lymphoid neoplasms and most human mononuclear cell subsets. In 2001, alemtuzumab was approved for marketing in the United States and Europe for use in patients with fludarabine-refractory chronic lymphocytic leukemia (CLL). ⋯ Alemtuzumab is frequently associated with acute 'first-dose' reactions when administered intravenously, but is much better tolerated when administered subcutaneously without loss of therapeutic efficacy. Additional potential adverse events associated with alemtuzumab administration include myelosuppression as well as profound cellular immune dysfunction with the associated risk of viral reactivation and other opportunistic infections. Additional studies detailing the mechanism of action of alemtuzumab as well as new strategies for prevention of opportunistic infections will aid in the future therapeutic development of this agent.
-
The vast majority of non-Hodgkin's lymphomas are of B-cell phenotype. Development of unlabeled or radiolabeled therapeutic monoclonal antibodies against the cell surface antigen, CD20, has revolutionized the treatment of these malignancies. It is clear that antibodies targeting other B-cell-specific molecules, such as CD22, also offer potential therapeutic benefit. ⋯ Data suggest that this agent is well tolerated, and can induce tumor regressions. Trials are currently evaluating its safety and activity in combination with rituximab (chimeric anti-CD20) and standard chemotherapy are ongoing. Initial results suggest that these regimens have acceptable toxicity, and that epratuzumab warrants further evaluation as an adjunct to standard lymphoma treatment regimens.
-
In the liver, several cell types have the longevity that is needed to be the cell of origin of a cancer: hepatocytes, cholangiocytes and progenitor cells. The latter are located in the most peripheral branches of the biliary tree, the ductules and canals of Hering. The most important risk factors for liver cancer are chronic viral hepatitis B and C and alcoholic and non-alcoholic steatohepatitis. ⋯ This makes it even more plausible that at least part of the hepatocellular carcinomas originate from a progenitor cell. Hepatocellular carcinomas expressing progenitor cell/ductular markers like cytokeratin 19 have a more aggressive clinical course. It is therefore important to recognize this entity.
-
Virotherapy is an approach for the treatment of cancer, in which the replicating virus itself is the anticancer agent. Virotherapy exploits the lytic property of virus replication to kill tumor cells. As this approach relies on viral replication, the virus can self-amplify and spread in the tumor from an initial infection of only a few cells. ⋯ A second strategy uses genetically modified viral vectors in which a cellular retargeting ligand is incorporated. A third strategy involves the construction of chimeric recombinant vectors, in which a capsid protein from one virus is exchanged for that of another. These transductional retargeting strategies have the potential for reducing deleterious side effects, and increasing the therapeutic index of virotherapeutic agents.
-
The most exciting advances in the tuberous sclerosis complex (TSC) field occurred in 1993 and 1997 with the cloning of the TSC2 and TSC1 genes, respectively, and in 2003 with the identification of Rheb as the target of tuberin's (TSC2) GTPase activating protein (GAP) domain. Rheb has a dual role: it activates mTOR and inactivates B-Raf. Activation of mTOR leads to increased protein synthesis through phosphorylation of p70S6K and 4E-BP1. ⋯ Despite these biochemical advances, exactly how mutations in TSC1 or TSC2 lead to the clinical manifestations of TSC is far from being understood. Two of the most unusual phenotypes in TSC are the apparent metastasis of benign cells carrying TSC1 and TSC2 mutations, resulting in pulmonary lymphangiomyomatosis, and the ability of cells with TSC1 or TSC2 mutations to differentiate into the separate components of renal angiomyolipomas (vessels, smooth muscle and fat). We will discuss how the TSC signaling pathways are affected by mutations in TSC1 or TSC2, focusing on how these mutations may lead to the renal and pulmonary manifestations of TSC.