Prospects of multidisciplinary research for development of new therapeutic modalities in India: preclinical research on brain tumors as an illustrative example

Preclinical research is an essential prerequisite for the development of new therapeutic modalities for different diseases. Close interactions between basic scientists and clinicians are important for rapid progress with optimum input of resources. Cancer is emerging as a very important health hazard in India. Brain tumors, particularly malignant gliomas present a unique challenge, because of their location within the limited space of skull compartment. Conventional adjuvant radiotherapy after surgery is ineffective in killing the residual tumour, and also leads to radiation necrosis in patients with prolonged survival. Therefore, several agents and their combinations are being investigated to enhance the radiation sensitivity of brain tumor cells. Malignant brain tumors are known to have significantly elevated glycolytic activity as compared to the corresponding normal tissues. Our earlier preclinical studies combining 2-deoxy-D-glucose (2-DG) with radiation showed that manifestation of damage was increased in several tumor cell systems, whereas it was reduced in the normal cells. These studies lead to clinical trials using radiation plus 2-DG on malignant gliomas. Lonidamine (LND), a selective inhibitor of glycolytic pathway in cancer cells has been used in clinical trials on patients with brain and several other types of malignant tumors. Recent studies from this laboratory on the combination of LND and 2-DG with other anticancer agents on malignant human glioma cell lines as well as cells derived from glioma biopsies will be described in this presentation. The role of multidisciplinary collaborations between basic scientists and clinicians in such studies will also be discussed. (author)