The Department of Biotechnology (DBT) is supporting National Institute of Mental Health and Neuro Sciences (NIMHANS) and Indian Institute of Science (IISc) along with Sathya Institute of Higher Medical Sciences (SSIHMS) with a grant of Rs. 6 crore for research in the field of brain cancer. The five-year research efforts from 2010 to 2015 is now in its last leg to uncover novel biomarkers and drug targets to tackle the brain cancer affecting scores of patients in the country.
Brain cancers are one of the top ten cancers among adults in India according to the ICMR Cancer Registry. Among these, gliomas are the commonest. Glioblastoma which is a WHO Grade IV glioma is the most malignant. Despite much research and understanding on glioblastomas, over the past few decades, the improvement in patient survival is only meager.
The project is an outcome of an earlier effort where NIMHANS teamed up with IISc and Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) to carry out translational research on gliomas. The tripartite research effort had focused on gene expression profiling and the team was able to identify novel diagnostic and prognostic biomarkers. Several patents were filed and the results were published in high impact cancer journals.
“The highlight of the research was deriving a 14 gene signature predicting survival of glioblastoma patients as well as a 16 gene classifier signature. Now, validation of these signatures in other patient cohorts would strengthen their clinical utility”, Dr Vani Santosh, professor of neuropathology, NIMHANS, told Pharmabiz.
Under the current research, NIMHANS and IISc are looking at other molecular aspects of gliomas such as the role played by epigenetic changes like DNA methylation and micro RNA (miRNA) mediated regulation of gene expression. Their study on global DNA methylation published in the journal titled Cancer Research identified a robust prognostic signature with potentials for risk stratification during treatment. The researchers also identified deregulated miRNAs in glioblastoma and showed miRNA involvement in glioma development, she added.
The teams are also engaged in the study of molecular genetic profile in peri-tumoural areas in order to comprehend the biology underlying tumour recurrence. The evaluation of the differential gene expression between the core and periphery of glioblastoma tumours is expected to reveal promising results, stated Dr. Santosh.
Further, the research is expanded to assess the genetic basis of radiation and chemo-resistance in glioblastomas and to identify serum biomarkers. Dedicated glioma labs at IISc under Prof. Kumaravel Somasundaram, department microbiology and cell biology and the team leader of the current DBT project, along with Prof Paturu Kondaiah, Chairperson, department of molecular reproduction, development and genetics, IISc, are also carrying out the functional characterisation of novel genes which could lead to identification of potential drug targets.
“Now what we identify as novel drug targets can be further pursued by the pharmaceutical companies engaged in the cancer drug discovery,” she said.
The Neuro-Oncology Lab at Neurobiology Research Centre, NIMHANS, headed by Dr Vani Santosh is fostered by investigators from the four departments of NIMHANS associated with the project which include Dr Yasha TC, Dept. of Neuropathology, Dr. Arivazhagan A and Dr Paritosh Pandey, Dept of Neurosurgery, Dr Rose Dawn and Dr Thennarasu K from departments of NIIR and Biostatistics along with dedicated PhD students and project assistants.