Role of immunohistochemistry in targeted cancer therapy (#15)
Chemotherapy which has been the standard therapeutic regimen for cancer has several disadvantages. These standard drugs fail to distinguish malignant versus normal tissue, resulting in a range of adverse effects. Targeted treatment modalities show a greater selectivity for tumor cells and causes less damage to normal cells. It is to be noted that morphologically distinct tumours show variable biological characteristics and response to treatment. It is thus becoming important to identify these targets within the cancer tissue which include the tumour cells and the tumour microenvironment (ie, stromal cells, microvessels, and host’s immune cells), all of which could serve as potential treatment targets.
Targets of tailored treatment are proteins involved in the cell-signaling pathway, cell cycle, apoptosis, and angiogenesis. Recent examples are detection of HER2 gene over-expression in breast and gastric cancers, mutations in several genes, i.e. EGFR for lung cancer, KRAS gene in lung / colo-rectal cancers, KIT gene in gastro-intestinal stromal tumor(GIST), detection of activated transduction signals for renal cell carcinoma, hormone receptors in neuroendocrine tumors. The agents used for this mode of treatment could include monoclonal antibodies, tyrosine kinase inhibitors, signal transduction inhibitors and hormonal analogues.
Most of these biomarkers were earlier detected by molecular techniques. These tests are expensive and not easily accessible. Immunohistochemistry is an excellent surrogate to identify the proteins / targets in question. Though widely used, this technique comes with its share of challenges which could be at the preanalytical, analytical and post analytical levels. It is highly mandatory to establish robust methodologies within the laboratory to obtain the right answer, which would ultimately benefit patient management / response to treatment.