ANTI-ADHESION Evolves To a Promising Therapeutic Concept in Oncology
Wednesday, April 9th, 2008.
Current Medicinal Chemistry. 2008;15(9):978-90. [Link]
Schmidmaier R, Baumann P.
Klinikum der Universität München, Medizinische Klinik Innenstadt, Abteilung Hämatologie und Onkologie, Ziemssenstr. 1, D-80336 München, Germany. ralf.schmidmaier@med.uni-munchen.de.
Abstract
Adhesion is a hallmark of haematological and solid cancer cells. All five classes of cell adhesion molecules (CAM) - integrins, cadherins, immunoglobulin-like CAMs, selectins and CD44s - are characteristically dysregulated in human cancer. Adhesion enables and promotes cancer-defining biological processes like growth, survival, migration, extravasation, homing, and metastasis. Furthermore, cell adhesion mediates drug resistance (CAM-DR) in multiple myeloma, malignant lymphoma, acute and chronic leukaemias, as well as in pancreatic cancer, neuroblastoma, small cell and non-small cell lung cancer, mesothelioma, colorectal carcinoma, and breast cancer. Cell adhesion protects from death by radiation, genotoxic chemotherapy, or targeted pathway inhibitors. Adhesion molecules are overexpressed on drug resistant cells (e.g. multiple myeloma or prostate cancer). Very recently, several cell adhesion mediated survival pathways have been elucidated, with key mediators being LFA-1, VLA-4, FAK, ILK, Src, PI3K, Akt, Ras, MEK, Erk, HMG-CoA reductase, Rho, Rho kinase, PKC, and NFkB. Because the surface and the intracellular targets are now known and because specific compounds are becoming increasingly available, first clinical trials regarding ANTI-ADHESION therapies are ongoing. However, in comparison to the comprehensive preclinical and clinical knowledge about CAMs, the number of drugs developed thus far is quite low. ANTI-ADHESION strategies include targeting of surface antigens, inhibition of cell adhesion associated pathways, inhibition of CAM-DR, and targeted drug delivery. As ANTI-ADHESION is based on general characteristics of cancer cells independent of specific disease entities or treatment modalities, it may become a successful, low-toxic and broadly applicable concept in cancer treatment.
Glossary
- prostate
- (pros-tate) a gland found only in men. It is just below the bladder and in front of the rectum. The prostate makes a fluid that is part of semen. The tube that carries urine, the urethra, runs through the prostate.
- metastasis
- (meh-tas-teh-sis) the spread of cancer cells to distant areas of the body by way of the lymph system or bloodstream.
- lymphoma
- (lim-foam-uh) a cancer of the lymphatic system, a network of thin vessels and nodes throughout the body. Its function is to fight infection. Lymphoma involves a type of white blood cells called lymphocytes. The two main types of lymphoma are Hodgkin's disease and non-Hodgkin's lymphoma. The treatment methods for these two types of lymphomas are very different.
- drug resistance
- refers to the ability of cancer cells to become resistant to the effects of the chemotherapy drugs used to treat cancer.
- chemotherapy
- (key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- carcinoma
- (car-sin-o-ma) a malignant tumor that begins in the lining layer (epithelial cells) of organs. At least 80% of all cancers are carcinomas.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
