The main areas of interest of Prof. Singh’s lab are understanding the mechanisms of carcinogenesis development to find novel targets which could be affected by natural agents, to inhibit cancer progression and metastasis. The laboratory’s efforts have been largely devoted towards not only screening natural compounds/ chemopreventive agents for their efficacy, but also providing mechanistic insights into their mode of action.
Discovering and evaluating anticancer activities of small molecules (phytochemicals) and providing scientific basis (mechanisms) for their effectiveness in controlling carcinogenesis is a priority area of research. The goal is to develop mechanism-based non-toxic anticancer agents for their potential use in cancer chemoprevention and treatment. The lab though in its early years of establishment has done significant work in studying natural compounds with anti-angiogenic efficacies. The laboratory has established good in vitro, in vivo and ex-vivo model systems to study modulation of tumor angiogenesis by these plant compounds.
Evaluating these phytochemicals for potential synergism with existing, well-established chemo-and radiotherapy regimens is also a significant focus of the lab.Along with these studies, the lab also tries to understand biological processes, which get deregulated during cancer development including mitogenic, and cell survival signaling, apoptosis and DNA damage/repair.
Other than mammalian cell-culture and rodent models, we are also working on establishing other model systems includingDrosophila Melanogaster model, which are easier for manipulation and would give us plausible explanations or cues that can be extrapolated to derive an understanding of the carcinogenesis development.
Development of cancer is a complex multistage process that involves distinct biochemical and cellular alterations. The conventional treatment approaches are limited by the toxicity to normal tissues and development of resistance over a period of time. Ionizing radiation has been implicated both in the carcinogenesis as well as a therapeutic strategy for cancer control. New advances in radiation biology have helped in decreasing the dosage and also in localizing the effects to the tumor. However, majority of malignant tumors develop resistance to radiation over a period of time mainly due to anomalous functioning of diverse biological pathways including RTK signaling, NF-kB pathway, sphingomyelinase pathway, DNA damage signaling, redox signaling, apoptosis, chromatin remodelling and epigenetic regulation. Acquired radioresistance hence becomes a vital setback in successful cancer treatment creating a critical need to look for adjuvant therapies.
The efficacy of radiation is further improved by use of various agents which sensitize the cells to radiation, thereby boosting the mortality rate sustained by radiation. To develop clinically relevant radiosensitizers requires an approach combining radiation with standard cytotoxic chemotherapeutic agents. However, even this becomes a risky set-up owing to the fact that these chemotherapeutic agents have their own set of side effects which needs to be counteredChemointervention has emerged lately as a novel approach in both preventing the disease as well as to increase the efficiency of the treatment modules presently in use. Naturally occurring compounds like curcumin, parthenolide, genistein, gossypol, ellagic acid, withaferin, plumbagin, etc., which are generally safe for normal cells, are known to possess anticancer properties and have been studied to show synergistic effect along with radio- and chemotherapy, in addition to showing protection to normal tissues. We focus on current theories regarding the molecular mechanisms mediating radiation resistance and the chemomodulatory effects of phytochemicals in ionization radiation-mediated cancer therapy.