[Kamat2010]

Biomarkers play a vital role in medicine as they give an idea about the severity of a disease with reference to the presence of the characteristics of any disease state that are identifiable and measurable. It actually indicates the physiological state of an organism by acting as an indicator of a particular state of disease. They help in the evaluation of various biological and pathogenic processes within an organism as well as the pharmacological response to therapeutics by objective measure including diagnostics and other imaging technologies. They give an idea about the drug action, drug metabolism and its efficacy as well as safety.

The development of cancer involves multiple stages such as genetic changes, epigenetic, cytogenetic as well as cell cycle changes. Hence, the advancement of different technologies that can help in the detection of the development of different stages may help in getting an in-depth understanding of the progression of cancer that may in turn help in the development of possible therapeutics for different types of cancer. Therefore, biomarkers play a very essential role in the detection, diagnosis, and prognosis of patient as well as the selection of personalized treatment for cancer.

The understanding of the pathways of the disease, the gene and protein targets of the disease have helped in the use of biomarkers in the different imaging technologies such as genomics, proteomics as well as genetics that are non-invasive in nature. The establishment of the exact relationship between the clinical pathology of cancer progression and the biomarkers can help in its early diagnosis and the prognosis of the patients by the clinical oncologists, which may further help in the development of patient specific treatment. The Human genome project has helped in the advancement of NDA sequencing studies with the development of microarrays, mass spectrometry, etc. that has helped in the expansion of the number of biomarkers available for different types of cancers. Some of the biomarkers that are used presently in the diagnostic as well as therapeutics for cancer are given below.

Cytogenetic markers: One of the markers for cancer is the different structural changes introduced in the chromosomes such as chromosomal aberrations. Somatic mutations in the reporter genes, oncogenes as well as the tumor suppressor genes have also proved to be a potent marker for cancer. Apart from them, specific changes in the transcriptomes are also being developed as biomarkers. E.g. the transcriptome marker based on the levels of exon-3 deleted variant isoform of proghrelin, the precursor of ghrelin, which is a growth factor associated with proliferation of prostrate cancer cells is being developed as a biomarker. The clonal and spatial heterogeneity analyses are the two main features of malignant tumors, which can be carried out by different histological, biochemical and cytometric methods.

Genetic markers: The transformation of the genes leading to gain or loss of function is associated with the formation of oncogenes. The random mutations that occur due to different factors in the regulatory region of the genes are responsible for this oncogenic transformation. In most of the cancers, genes act as potent biomarkers that help in the diagnosis as well as gene-based therapy of the disease. Gene deletions may also help in the development of the disease. These changes within the genes can be identified using PCR techniques as well as Microsatellite probes as microsatellite instability or alterations is one of the changes evident in preneoplastic stage of tumor cells. The Adenomatous polyposis gene (APC) is associated with the suppression of cancer, which is altered in the carcinoma patients by somatic mutation, hypermethylation or production of short and non-functional APC protein.

Epigenetic markers: Epigenetic changes are usually associated with modification in the gene expression patterns that result due to changes in the histone proteins associated with DNA by methylation, acetylation or phosphorylation. The hypomethylation of genomes is associated with instability of the genomes as well as stronger gene expression, while hyper methylation in the CpG island promoter is associated with the silencing of the functions of the tumor suppressor genes such as apoptotic genes, metastatic genes as well as biotransformation and signal transduction genes. Hypermethylation and aberrant methylation has been used as a biomarker in many carcinomas. The research in the field of epigenetics has helped in increasing the rate of survival with some form of leukaemias as well as lymphomas with the use of drugs that help in the alteration of DNA methylation and histone acetylation. However, the development of drugs or therapeutics that may help in the reversal of the epigenetic changes remain to be seen in near future.