[Kamat2010]

Biomarkers for cancer prognosis and diagnosis –II
Apart from the most common biomarkers such as cytogenetic, genetic, and epigenetic biomarkers, other biomarkers involved in the cancer diagnosis and prognosis as summarized by Bhatt et al. from the Institute of Nuclear Medicine & Allied Sciences are as follows:

I. Biomarkers in the form of cells: In the advanced stages of cancer, the appearance of different types of cells is seen in the bloodstream leading to easy monitoring. In some types of cancers, it has been found that tumour and immune cells have become effective biomarkers for the development of prognosis for the disease, while in some other types of cancer, their role remains to be elucidated. The circulating tumor cells (CTCs) have proved to be powerful biomarkers for Breast cancer as their elevation in the blood circulation is related to the progression of the disease, while their elimination is associated with the effectiveness of the cancer therapy. T-regulatory cells (T-regs) are potent biomarkers as increased number of T-regs is found in the blood stream or tumors of patients of lung, breast, skin, liver cancers. FoxP3, the transcription factor of T-regs is an intracellular biomarker for tumors.

II. Viral biomarkers: Hepatocellular carcinoma (HCC) is one of the diseases that are induced by virus. Hepatitis B virus is a potent biomarker for HCC, while human papillomaviruses are good biomarkers for cervical cancer. Epstein-Barr virus (EBV) is also associated with carcinogenesis with the EBV DNA serving as marker for nasopharyngeal carcinoma and Hodgkin’s lymphoma.

III. Cancer antigens as biomarkers: The cancer cells are responsible for the secretion of different bio molecules that result in the bloodstream or other cellular fluid and serve as biomarkers for different types of cancers. Some of the well-known cancer antigens are:

a. Prostate specific antigen (PSA) for prostate cancer,
b. Alpha fetoprotein that are actively secreted during the foetal life by the hepatocytes i.e. liver cells in case of endodermal sinus tumor, hepatoblastoma, HCC, neuroblastoma, etc.
c. CA125 expressed in epithelial ovarian cancers,
d. CA15-3, which are elevated in breast cancer,
e. CA19-9, a tumor marker for diagnostic purpose in pancreatic cancer
f. Carcinoembryogenic antigen (CEA) that is elevated in colorectal, breast, pancreatic, lung cancers as well as smokers.
g. Human Chorionic Gonadotropin, elevated in ovarian and testicular cancers
h. Thyroglobulin, in papillary and follicular thyroid cancer
i. Heat Shock proteins associated with cell proliferation and growth and hence elevated in tumors.
j. Oral fluid contain proteins, which are biomarkers for oral cancer
k. Mitochondrial markers as the mutated DNA of mitochondria prove to be markers for cancer and in most of the cases more potent than mutated p53.

IV. Metabolic biomarkers: The BEC index i.e. Bioenergetic index has been developed for the prognosis of cancer as it gives an idea about the glucose metabolic pathways such as glycolysis as well as the expression of metabolic enzymes, which are increased during the progression of tumor growth, oncogenic transformation as well as impairment of the functionality of cells. Thus, the utilization of glucose proves to be a potent metabolic marker for diagnosis, prognosis, as well as tumor response to different therapeutics.

V. Therapeutic biomarkers: In-depth studies related to Cancer have helped in the development of different therapeutics targeting the molecular mechanism of cancer involved in the progression of the disease as well as apoptosis.

a. Glycolysis metabolism is a biomarker as the glycolytic inhibitors with radiotherapy have helped in increasing the survival rate in brain tumor patients.
b. mTOR (mammalian target of ropamycin): serine-threonine protein kinase involved in cell proliferation with roles in translation, ribosome biogenesis and reorganization of actin cytoskeleton and autophagy inhibition. Ribosomal protein S6 is a biomarker as its levels show the sensitivity of mTOR inhibitor,
c. Telomerase is a good marker for malignant tumors. Inhibitors of telomerase help in inhibiting tumor growth.
d. p53 is a potent biomarker as its targeting is essential in the stimulation of apoptosis and hence, targeted in different therapeutics for cancer.
e. Tyrosine kinases are potent targets for cancer therapies. Their over expression has been associated with different types of cancer such as breast cancer and other solid cancers. Hence, the inhibitors of the enzyme that block the binding of ATP with the enzyme thereby blocking the receptors on cell surface of tumor cells help in preventing cell proliferation and growth thereby their inhibitors can be used as potent anticancer agents.
f. HDACs (Histone deacetylases) have been associated with tumorogenesis as it is involved in the regulation of the expression of some tumor suppressor genes and leads to excess proliferation and oncogenesis. Hence, their inhibitors can help in the gene modulation and regulation of biological pathways.
g. Role of Pin 1 i.e. peptidyl prolyl isomerase in cancer growth has been elucidated by its over expression in breast cancer cell lines and tissues. One of its substrates is phosphorylated p53, which has opened the gates for the targeting of this protein in anticancer therapeutics.

Thus, the development in the field of genomics and proteomics has helped in the discovery of a number of biomarkers that would help in the easy diagnosis, prognosis, as well as the response of the tumor cells to therapy. The relevance of biomarkers supported by concrete evidence would help to provide direction to the future development of different alternative therapies for the disease that would help cure the fatal diseases.