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  Cancer Biology and related Areas
Cancer Biology research in CDRI focuses on breast, cervical, oral, and prostate and blood cancers with the following objectives:
·  Creation of appropriate platform for interdisciplinary collaborative research
 · Creation of knowledge base in Cancer Biology
 · Lead identification/optimization to obtain drug-like molecules

 
BASIC RESEARCH
•
 Studies on molecular mechanisms of chemo resistance in breast cancers.
•
 Molecular studies on redox regulation in breast cancers (Figure-1).
•
 Studies on genomic profiling of cancers in North Indian population.
•
 Proteomics based therapeutic target validation in breast cancer (Figure-2).
•
 Studies on molecular mechanisms of selective estrogen receptor modulator action in cancer cells.
•
 Elucidation of anti cancer drug action in patient derived primary cell culture systems.
•
 Studies on identification of molecular targets of anticancer drug action using yeast as a model system
DRUG DESIGH AND SYNTHESIS
•
 Anti-cancer compounds based on rational approaches of drug design including CADD & virtual screening.
•
 2D & 3D-QSAR based predictive models for the design of novel anti-cancer agents.
•
 Natural product inspired scaffolds as Anti-cancer agents.
•
 Design of biologically active anticancer peptides.
 
SCREENING AND DRUG DEVELOPMENT
•
 In vitro cell based and high throughput screening.
    •  Ovarian Cancer, Breast Cancer, Oral Cancer
    •  Prostate Cancer, Cervical Cancer, Blood Cancer
•
 In vitro screening of drugs in primary patient derived chemo resistant cells.
•
 Development of in vivo mouse models for screening of active molecules.
Figure-1
Studies on Redox Regulation in Carcinogenesis
Aberrant Redox regulation induces oxidative stress in the cellular micro environment leading to modification of cell signaling pathways and initiation of carcinogenesis. Ongoing studies aim to understand regulation redox pathways and their influence on cell survival and carcinogenesis.
 
Figure-2
Proteomics based approach for therapeutic Target validation in breast cancer
Antibreast cancer drug (T) induces Estrogen Receptor (ER) to undergo a conformational change that targets the receptor for interaction with both coactivators (CoA=????) and corepressors (CoR=???). Unopposed coactivators enhance transcription at specific loci, leading to an increased agonist activity and drug resistant phenotype. The increased corepressor level blocks transcription and maintains the drug-sensitive phenotype. In addition other pathways (=????) may also be activated/inhibited upon by drugs. The proteomic based approach aims to validate novel drug /therapeutic targets
 
Significant achievements
•
 Patient derived primary cultures for drug screening developed.
•
 FRET assays for screening of small anti-cancer molecules developed.
•
 In vitro cell based assays for screening of nuclear receptors developed.
•
 Proteomic screening of anticancer agents standardized.
 
Recent Publications
•
 GPS2 is required for cholesterol efflux by triggering histone demethylation, LXR recruitment, and coregulator assembly at the ABCG1 locus. (2009) Jakobsson T, Venteclef N, Toresson G, Damdimopoulos AE, Ehrlund A, Lou X, Sanyal S, Steffensen KR, Gustafsson JA, Treuter E. Mol Cell. 2009 May 14;34(4):510-8.
•
 Breast cancer risk associated with polymorphisms of IL-1RN and IL-4 gene in Indian women. (2009) Konwar R, Chaudhary P, Kumar S, Mishra D, Chattopadhyay N, Bid HK.Oncol Res. 2009;17(8):367-72.
•
 Staurosporine induces apoptosis in human papillomavirus positive oral cancer cells at G2/M phase by disrupting mitochondrial membrane potential and modulation of cell cytoskeleton.(2009)Sarkar J, Singh N, Meena S, Sinha S.Oral Oncol. PMID: 19502099
•
 Centchroman induces G0/G1 arrest and caspase-dependent apoptosis involving   mitochondrial membrane depolarization in MCF-7 and MDA MB-231 human breast cancer cells. ( 2008)Nigam M, Ranjan V, Srivastava S, Sharma R, Balapure AK. Life Sci. 2008 Mar 12;82(11-12):577-90
•
 Molecular iodine induces caspase-independent apoptosis in human breast carcinoma cells involving the mitochondria-mediated pathway. (2006) Shrivastava A, Tiwari M, Sinha RA, Kumar A, Balapure AK, Bajpai VK, Sharma R, Mitra K, Tandon A, Godbole MM.J Biol Chem. 2006 Jul 14;281(28):19762-71
•
 Mechanism of 4-HPR-induced apoptosis in glioma cells: evidences suggesting role of mitochondrial-mediated pathway and endoplasmic reticulum stress.(2006)Tiwari M, Kumar A, Sinha RA, Shrivastava A, Balapure AK, Sharma R, Bajpai VK, Mitra K, Babu S, Godbole MM.Carcinogenesis. 2006 Oct;27(10):2047-58.
•
 Multiple ways of C/EBPalpha inhibition in myeloid leukaemia. Trivedi AK, Pal P, Behre G, Singh SM.Eur J Cancer. 2008 Jul;44(11):1516-23
•
 Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPalpha by inhibiting its ubiquitination.(2007) Trivedi AK, Bararia D, Christopeit M, Peerzada AA, Singh SM, Kieser A, Hiddemann W, Behre HM, Behre G. Oncogene. (2007) 26(12):1789-801
•
 Isoniazid induces oxidative stress, mitochondrial dysfunction and apoptosis in Hep G2 cells. (2007) Bhadauria S, Singh G, Sinha N, Srivastava S. Cell Mol Biol  15;53(1):102-14.
 
 
Cancer Biology Research Group
 
Screening Generation of in vivo models and testing of lead molecules
•
 Dr. D. P. Mishra
•
 Dr. J Sarkar Validation of specific biomarkers in north Indian scenario by proteomics, genomics and epigenetic approaches

Lead identification/optimization
•
 Dr. D. P. Mishra
•
 Dr. A. K. Trivedi
•
 Dr P M S Chauhan Primary Cell culture in 3D systems
•
 Dr K V Sashidhara
•
 Dr. D. P. Mishra
•
 Dr. S. Sanyal

Mechanism of action of lead molecules
• Dr. S. Sanyal • Dr S K Rath
• Dr Arun Trivedi • Dr Kalyan Mitra
•
 Dr Ritu Raj Konwar • Dr A K Balapure
• Dr Shakil Ahmed  
 
 
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