Targeted cancer therapy is founded on the premise of targeted detection of diagnostic molecular markers that are usually mutated and/ or over-expressed proteins. This represents a shift in clinical diagnostics away from morphological parameters like tumor size, grade and stage that have traditionally served as the foundation for cancer diagnostics. Morphological assessments fail to address the genetic heterogeneity that is increasingly becoming an understood and appreciated aspect of all cancers.
Patient stratification at the molecular level is a necessity to advancing cancer treatments to a state of personalized therapy. Reverse Phase Protein Microarrays (RPPA) are expounding on the information obtained from RNA transcript profiling by illuminating the ramifications of post translational modifications and their effects on the complexity of protein networks in cancerous cells.
When applied to Formalin Fixed Paraffin Embedded (FFPE) tissue samples, RPPA enables a more comprehensive measurement of proteins than is possible with classical immunohistochemical methods. This advanced methodology is improving our understanding of cell signaling pathways in all cancers. Deregulated pathways provide a point of intervention for targeted cancer therapies that is radically different from traditional chemotherapeutic treatments.
Traditional cancer therapeutics like chemotherapy are cytotoxic in nature; they target entire cells rather than specific molecules. By targeting deregulated pathways, the opportunity for new non-cytotoxic treatments becomes a reality. Many targeted cancer therapies enact their effects by cytostatic rather than cytotoxic means. Cytostatic treatment methods that block proliferation offer patients a regimen with less debilitating side effects. By interacting with individual molecules in a signaling cascade, tumor proliferation can be effectively inhibited. The impressive element of targeted therapy lies in the fact that cancer can now be treated by precisely targeting identified molecular candidates for intervention rather than using compounds that target entire cells for death.
Targeted cancer therapeutics can be divided into two categories: small molecules and monoclonal antibodies. Small molecules easily enter the cell and are therefore used for intracellular targets. Monoclonal antibodies are too large to diffuse or be actively transported across the membrane and are used for targets bound to the cell’s extracellular surface.
A variety of targeted therapies are FDA approved. Hormone therapies are targeted strategies that limit the quantity of hormones produced in patients with cancers that are hormone dependent for growth. This is a popular method of breast cancer treatment. Other therapies include signal transduction inhibitors, gene expression modulators, apoptosis inducers, immunotherapies, angiogenesis inhibitors and toxin delivery molecules. These targeted therapies work by mechanisms that include prevention of target binding to receptors to prevent receptor activation and reduction of target molecule activity.
Targeted cancer therapies do have limitations and there is a need to develop methods for expedited target detection from patient tissue samples. Targeted therapies also demand the identification of qualified targets that play an instrumental role in cell growth, proliferation and survival. Additionally, cancer cells develop resistance to targeted therapeutics. The target can become mutated, resulting in loss of recognition by the therapeutic. The tumor can also develop new pathways to grow and proliferate that are non-in on the targeted molecules.