Are there limitations with 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 (1).  
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.