Targeted Therapies for Cancer

Targeted therapies act on specific molecular targets that are associated with cancer, whereas most standard chemotherapies act on all rapidly dividing normal and cancerous cells.

Targeted therapies are deliberately chosen or designed to interact with their target, whereas many standard chemotherapies were identified because they kill cells.

Immunotherapies trigger the immune system to destroy cancer cells. Some immunotherapies are monoclonal antibodies that recognize specific molecules on the surface of cancer cells. Binding of the monoclonal antibody to the target molecule results in the immune destruction of cells that express that target molecule. Other monoclonal antibodies bind to certain immune cells to help these cells better kill cancer cells.

Apoptosis Inducers cause cancer cells to undergo a process of controlled cell death called apoptosis. Apoptosis is one method the body uses to get rid of unneeded or abnormal cells, but cancer cells have strategies to avoid apoptosis. Apoptosis inducers can get around these strategies to cause the death of cancer cells.

Gene Expression Modulators modify the funcation of proteins that play a role in controlling gene expression.

Signal Transduction Inhibitors block the activities of molecules that participate in signal transduction, the process by which a cell responds to signals from its environment. During this process, once a cell has received a specific signal, the signal is relayed within the cell throught a series of biochemial reactions that ultimately produce the appropriate response(s). In some cancers, teh malignant cells are stimulated to adivide continuously without being promoted to do so by external growth factors. Signal transduction inhibitors interfere with this inappropriate signaling. 

Angiogenesis Inhibitors block the growth of new blood vessels to tumors (a process called tumor angiogenesis). A blood supply is necessary for tumors to grow beyond a certain size because blood provides the oxygen and nutrients that tumors need for continued growth. Treatments that interfere with angiogenesis may block tumor growth. some targeted therapies that inhibit angiogenesis interfere with the action of vascular endothelial growth factor (VEGF), a substance that stimulates new blood vessel formation. Other angiogenesis inhibitors target other moledules that stimulate new blood vessel growth. 

Monoclonal Antibodies that Deliver Toxic Molecules can cause the death of cancer cells specifically. Once the antibody has bound to its target cell, the toxic molecule that is linked to the antibody – such as radioactive substance or a poisonous chemical – is taken up by the cell, ultimately killing that cell. The toxin will not affect cells that lack the target for the antibody – i.e. the vast majority of cells in the body.

What are the limitations of targeted cancer therapies?

Targeted therapies do have some limitations. One is that cancer cells can become resistant to them. Resistance can occur in two ways: the target itself changes through mutation so that the targeted therapy no longer interacts well with it, and/or the tumor finds a new pathway to achieve tumor growth that does not depend on the target.

For this reason, targeted therapies may work best in combination. For example, a recent study found that using two therapies that target different parts of the cell signaling pathway that is altered in melanoma by the BRAF V600E mutation slowed the development of resistance and disease progression to a greater extent  than using just one targeted therapy.    

Another approach is to use a targeted therapy in combination with one or more traditional chemotherapy drugs. For example, the targeted therapy trastuzumab (Herceptin®) has been used in combination with docetaxel, a traditional chemotherapy drug, to treat women with metastatic breast cancer that overexpresses the protein HER2/neu.

Another limitation of targeted therapy at present is that drugs for some identified targets are difficult to develop because of the target’s structure and/or the way its function is regulated in the cell. One example is Ras, a signaling protein that is mutated in as many as one-quarter of all cancers (and in the majority of certain cancer types, such as pancreatic cancer). To date, it has not been possible to develop inhibitors of Ras signaling with existing drug development technologies. However, promising new approaches are offering hope that this limitation can soon be overcome.