About Dr. Raju
Dr. Uma Raju is a Research Assistant Professor in the Department of Experimental Radiation Oncology since March 2005. The focus of her research is to improve the outcome of chemo-radiation therapy by identifying the markers of resistance and targeting them using molecularly targeted agents. Her focus is on receptor tyrosine kinases and related kinases that are abnormally active in malignant tissues. Dr. Raju has completed 2 funded studies where she served as the PI and several other projects where she serves as a co-investigator. Currently, she serves as a PI in two ongoing project funded by EMD Serono Merck and completion of this project may lead to a clinical study designed based on her preclinical findings. Such translational potential made possible due to her collaboration with Dr. KK. Ang (a leading Radiation Oncologist). Her association with other clinician scientists at M.D. Anderson extends to Drs. J. Heymach and L. Byers (Biomarker Profiling studies), Z. Liao (novel Chinese drug study), and J. Welsh (c-Met inhibitor study). Outside M.D. Anderson, she had been conducting collaborative studies with Drs. C. Ha (UT, San Antonio) and MD. Story (UT South Western, Dallas) on the modulation radiation sensitization of lymphomas. Proteomics studies were conducted in collaboration with Drs. P. Lukas and I. Skvortsova of Department of Therapeutic Radiology & Oncology, Innsbruck, Austria. Dr. Raju is known for her expertise in pre-clinical evaluation of novel molecularly targeted therapeutic agents and the underlying mechanisms in enhancing radiation therapy outcome.
Assistant Professor, Department of Department of Experimental Radiation Oncology, UT MD Anderson Cancer Center, Houston, TX
More than 50% of cancer patients undergo chemo-radiation therapy as part of their treatment regimen for upper aero-digestive tract cancers, such as head and neck and lung cancers. However, the cure rate is still low and there is a need for novel treatment strategies to improve treatment outcome. My research interest is to test the hypothesis that targeting molecules whose functions are well regulated in normal cells but deregulated in cancer cells will improve tumor response with a better therapeutic gain. My investigation include preclinical evaluation of several molecularly targeted agents: (1) cetuximab, an anti- EGFR antibody, (2) celecoxib, an inhibitor of COX-2, (3) flavopiridol, an inhibitor of cdks, (4) BMS-599626 and BMS-690514, pan-EGFR family inhibitors, (5) XL-844, an inhibitor of Chk kinases, (6) Dasatinib (BMS-354825), an inhibitor of Src family kinases, (7) XL-228, an inhibitor of cSrc, IGF-1R and aurora kinases, (8) IMC-A12, an anti-IGF-1R antibody, (9) Cilengitide, an inhibitor of two of the integrins, and (10) EMD1214063, an inhibitor of c-Met. The experimental cancer model systems used in these studies comprised many responders and non-responders to the above mentioned agents in combination with radiation or chemotherapy. Using these systems identification of markers of response/resistance to therapy is ongoing through profiling studies by proteomics and genomics. My focus is mainly on two sets of factors: (1) identification of cellular proteins and/pathways in DNA repair that are responsible for the resistant phenotype of cancer cells and (2) characterization of cancer stem cell markers that are involved in the resistance as well as recurrence and metastatic spread.
|1982||Madurai Kamaraj University, Madurai, IND, PHD, Biology|
|1976||Madurai University, Madurai, IND, MS, Zoology|
|1974||Madurai University, Madurai, IND, BS, Biology and Chemistry|
Instructor, Department of Department of Experimental Radiation Oncology, Division of Radiation Oncology, UT M. D. Anderson Cancer Center, Houston, TX, 2002 - 2005
Research Associate, Department of Department of Experimental Radiation Oncology, Division of Radiation Oncology, UT M. D. Anderson Cancer Center, Houston, TX, 2000 - 2001
- Mason KA, Raju U, Buchholz TA, Wang L, Milas ZL, Milas L. Poly (ADP-ribose) polymerase inhibitors in cancer treatment. Am J Clin Oncol 37(1):90-100, 2014. e-Pub 2012. PMID: 22495455.
- Deorukhkar A, Ahuja N, Mercado AL, Diagaradjane P, Raju U, Patel N, Mohindra P, Diep N, Guha S and Krishnan S.. Zerumbone increases oxidative stress in a thiol-dependent ROS-independent manner to increase DNA damage and sensitize colorectal cancer cells to radiation. Cancer Medicine 10.1002/cam4.367:1-15, 2014. PMID: 25450478.
- Raju U, Molkentine DP, Valdecanas DR, Deorukhkar A, Mason KA, Buchholz TA, Meyn RE, Ang AA and Skinner H.. Inhibition of EGFR or IGF-1R signaling enhances radiation response in head and neck cancer models but concurrent inhibition has no added benefit. Cancer Medicine 10.1002/cam4.345:1-10, 2014. PMID: 25355701.
- Wang Z-Q, Johnson C, Kumar A, Molkentine DP, Molkentine JM, Rabin T, Mason KA, Milas L and Raju U.. Inhibition of P-TEFb by DRB Suppresses SIRT1/CK2α Pathway and Enhances Radiosensitivity of Human Cancer Cells. Anticancer Research 34:6981-6989, 2014. PMID: 25503124.
- Matsumoto F, Valdecanas DN, Mason KA, Milas L, Ang KK, Raju U. The impact of timing of EGFR and IGF-1R inhibition for sensitizing head and neck cancer to radiation. Anticancer Research 32(8):3029-35, 2012. PMID: 22843870.
- Torres MA, Raju U, Molkentine D, Riesterer O, Milas L, Ang KK. AC480, formerly MS-599626, a pan Her inhibitor, enhances radiosensitivity and radioresponse of head and neck squamous cell carcinoma cells in vitro and in vivo. Invest New Drugs 29(4):554-61, 2011. e-Pub 2010. PMID: 20119866.
- Skvortsova I, Skvortsov S, Raju U, Stasyk T, Riesterer O, Schottdorf EM, Popper BA, Schiestl B, Eichberger P, Debbage P, Neher A, Bonn GK, Huber LA, Milas L, Lukas P. Epithelial-to-mesenchymal transition and c-myc expression are the determinants of cetuximab-induced enhancement of squamous cell carcinoma radioresponse. Radiother Oncol 96(1):108-15, 2010. e-Pub 2010. PMID: 20451273.
- Skvortsova I, Skvortsov S, Stasyk T, Raju U, Popper BA, Schiestl B, von Guggenberg E, Neher A, Bonn GK, Huber LA, Lukas P. Intracellular signaling pathways regulating radioresistance of human prostate carcinoma cells. Proteomics 8(21):4521-33, 2008. e-Pub 2008. PMID: 18821526.
- Dittmann KH, Mayer C, Ohneseit PA, Raju U, Andratschke NH, Milas L. Celecoxib induced tumor cell radiosensitization by inhibiting radiation induced nuclear EGFR transport and DNA-repair: a COX-2 independent mechanism. Int Journal Radiat Oncol Biol Physics 70(1):203-212, 2008. e-Pub 2007.
- Wiedenmann N, Koto M, Raju U, Milas L, Mason KA. Modulation of tumor radiation response with G3139, a bcl-2 antisense oligonucleotide. Invest New Drugs 25(5):411-416, 2007. e-Pub 2007. PMID: 17492397.
- von Holzen U, Pataer A, Raju U, Bocangel D, Vorburger SA, Liu Y, Lu X, Roth JA, Aggarwal BB, Barber GN, Keyomarsi K, Hunt KK, Swisher SG. The double-stranded RNA-activated protein kinase mediates radiation resistance in mouse embryo fibroblasts through nuclear factor kappaB and Akt activation. Clin Cancer Res 13(20):6032-9, 2007. PMID: 17947465.
- Apisarnthanarax S, Alauddin MM, Mourtada F, Ariga H, Raju U, Mawlawi O, Han D, Bornmann WG, Ajani JA, Milas L, Gelovani JG, Chao KS. Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models. Clin Cancer Res 12(15):4590-7, 2006. PMID: 16899606.
- Raju U, Ariga H, Koto M, Lu X, Pickett J, Valdecanas D, Mason KA, Milas L. Improvement of esophageal adenocarcinoma cell and xenograft responses to radiation by targeting cyclin-dependent kinases. Radiother Oncol 80(2):185-191, 2006. PMID: 16905211.
- Milas L, Raju U, Liao Z, Ajani J. Targeting molecular determinants of tumor chemo-radioresistance. Semin Oncol 32(6 Suppl 9):S78-81, 2005. PMID: 16399438.
- Raju U, Ariga H, Dittmann K, Nakata E, Ang KK, Milas L. Inhibition of DNA repair as a mechanism of enhanced radioresponse of head and neck carcinoma cells by a selective cyclooxygenase-2 inhibitor, celecoxib. Int J Radiat Oncol Biol Phys 63(2):520-8, 2005. PMID: 16168844.
- Ismail SM, Puppi M, Prithivirajsingh S, Munshi A, Raju U, Meyn RE, Buchholz TA, Story MD, Brock WA, Milas L, Thames HD, Stevens CW. Predicting radiosensitivity using DNA end-binding complex analysis. Clin Cancer Res 10(4):1226-34, 2004. PMID: 14977819.
- Raju U, Yeung SJ, Eskin A. Involvement of proteins in light resetting ocular circadian oscillators of Aplysia. Am J Physiol 258(1 Pt 2):R256-62, 1990. PMID: 2154135.
- Raju U, Riesterer O, Wang ZQ, Molkentine DP, Molkentine JM, Johnson FM, Glisson B, Milas L, Ang KK. Dasatinib, a multi-kinase inhibitor increased radiation sensitivity by interfering with nuclear localization of epidermal growth factor receptor and by blocking DNA repair pathways. Radiother Oncol 105(2):241-9. e-Pub 2012. PMID: 23010482.
- Deorukhkar AA, Molkentine DP, Valdecanas DR, Mason KA and Raju U.. Pre-clinical evaluation: efficacy of DI17E6, a therapeutic antibody against alpha v integrins, compared to cilengitide in sensitizing human cancers to radiation therapy. AACR, 2014.
- Raju U, Molkentine DP, Valdecanas DR, Deorukhkar AA, Mason KA, Buchholz TA, Meyn RE and Skinner H.. Inhibition of IGF-1R signaling enhances the head and neck tumor radioresponse but fails to further improve tumor response to cetuximab and radiation therapy in vivo. ASTRO, 2014.
- Raju U, Molkentine DP, Molkentine JM, Valdecanas DN, Ang KK.. Targeting Met signaling to overcome human cancer cell resistance to radiation. AACR, 2013.
- Bhardwaj A, Ganesan N Molkentine D, Raju U and Bedrosian I.. miR-34a as a radio sensitizer of triple negative breast cancer. AACR, 2013.
- Wang L, Valdecanas D, Molkentine D, Milas L, Mason KA, Ang KK, Raju U. Tumor microenvironment and integrins as effective targets to improve radiotherapy outcome. ICTR, 2012.
- Raju U, Molkentine D, Valdecanas D, Ang KK. Schedule dependent tumor cell response to radiation (IR) when combined with anti-IGF1R and anti-EGFR antibodies. EORTC-NIH-AACR, 2012.
- Wang L, Valdecanas D, Molkentine D, Milas L, Mason KA, Ang KK, Raju U. Inhibition of αvβ3 and αvβ5 integrins by cilengitide improved tumor response to radiation in human head and neck squamous cell carcinoma and non-small cell lung cancer models. ICRR, 2011.
- Matsumoto F, Molkentine D, Clary DO, Milas L, Ang KK, Raju U. A multi-kinase inhibitor, XL228, enhanced human cancer cell radiosensitivity and suppressed cell invasion and migration. AACR, 2011.
- Raju U, Matsumoto F, Molkentine D, Milas L, Ang KK.. Co-targeting EGFR and IGF1R to sensitize or overcome induced resistance of head and neck cancer models to radiation. AACR, 2011.
- Matsumoto F, Raju U, Valdecanas D, Milas L, Ang KK. Triple agent therapy combining radiation with AMG479 (IGF1R antibody) and panitumumab (EGFR antibody) in a head and neck tumor model. AACR, 2011.
- Wang L, Valdecanas D, Molkentine D, Milas L, Mason KA, Ang KK, Raju U. Preclinical evaluation of the effects of cilengitide, an inhibitor of integrins, in sensitizing human solid cancer xenografts to radiation. AACR, 2011.
- Matsumoto F, Raju U, Molkentine D, Ang KK, Milas L.. cSrc is a radioresistance molecule in cancer therapy: cSrc-siRNA transfection augments tumor cell radiosensitivity in vitro and chemical inhibition of Src kinases increases tumor response to radiation. AACR, 2010.
- Wang L, Milas L,Raju U, Molkentine D, Yang P, Cohen L, Liao Z. Huachansu, an extract from toad skin strongly enhances radiosensitivity of human lung cancer lines. AACR, 2010.
- Sano D, Matsumoto F, Valdecanas DR, Zhao M, Molkentine DP, Papadimitrakopoulou V, Heymach J, Raju U, Milas L, Myers JN. Treatment with vandetanib can overcome resistance of head and neck squamous cell carcinoma cells to cisplatin and radiation in an orthotopic animal model. AACR, 2010.
- Riesterer O, Yang Q, Raju U, Tucker S, Valdecanas D, Carpenter J, Pickett J, Wang L, Ang K, Milas L.. Enhancement in local tumor control and reduction in distant metastases of human tumor xenografts by combining radiotherapy with anti-EGFR (C225) and anti-VEGFR-2 (DC101) antibodies. AACR, 2009.
- Raju U, Riesterer O, Pickett J, Molkentine D, Giri U, Milas L.. A novel Chk inhibitor, XL844, increases human cancer cell radiosensitivity through promotion of mitotic catastrophe. AACR, 2009.
- Wang Z, Raju U, Molkentine D, Milas L. Inhibition of RNA polymerase II activity enhances radiosensitivity of human non-small cell lung carcinoma in vitro. AACR, 2009.
- Raju U, Johnson F, Glisson B, Riesterer O, Milas L, Ang KK.. Mechanisms of enhanced radiosensitivity of human head and neck squamous cell carcinomas by dasatinib (BMS-354825, an inhibitor of Src kinases) include induction of apoptosis and inhibition of DNA repair. AACR, 2008.
- Torres M, Raju U, Milas L, Ang KK.. A pan Her inhibitor, BMS-599626, augments radiosensitivity of head and neck squamous carcinoma cells (HNSCC) in vitro and increases HNSCC tumor radioresponse in vivo. AACR, 2008.
- Riesterer O, Pickett J, Patel N, Raju U, Hicklin D, Ang K, Milas L.. Tumor Bed Irradiation Enhances Sensitivity of A431 Tumor Xenografts to C225 anti-EGFR Antibody. AACR, 2008.
- Raju U, Koto M, Johnson F, Glisson B, Milas L and Ang KK.. Molecular determinants of head and neck squamous cell carcinoma radioresistance: a novel treatment strategy to improve radiotherapy outcome. AACR, 2007.
- Torres M, Raju U, Milas L and Ang KK.. A pan Her inhibitor, BMS-599626, augments radiosensitivity of HN5 cells by increasing radiation-induced apoptosis and inhibiting DNA repair. AACR, 2007.
- Raju U, Koto M, Pickett J, Hittelman W, Ajani JA and Milas L.. Repression of transcription via cyclin-dependent kinase-9 inhibition is associated with flavopiridol - induced enhancement of radiosensitivity of human esophageal adenocarcinoma cells. AACR, 2006.
- Raju U, Ariga H, Ajani A and Milas L.. Targeting cyclin-dependent kinases to improve treatment efficacy of radiation and docetaxel for esophageal carcinomas. AACR, 2005.
- Bocangel DB, von-Holzen U, Chada S, Pataer A, Takada Y, Raju U, Aggarwal BB, Barber GN, Chiao P, Milas L, Hunt KK and Swisher SG.. Threshold for radiation sensitization induced by adenoviral delivery of TNF-alpha: Role of the double stranded RNA activated protein kinase (PKR). AACR, 2005.
- Suh Y-J, Raju U, Chada S, McKenzie T, Liu Y, Swisher SG, Lucci A and Hunt KK.. Enhanced radiosensitization of breast cancer cells in vitro by combining Adenovirus-mediated delivery of melanoma differentiation-associated gene-7 (Ad-mda7) and celecoxib. AACR, 2005.
- Ariga H et al. Flavopiridol enhances radiosensitivity of human head and neck, and esophageal carcinoma cells. AACR, 2004.
- Raju U, Ariga H, Valdecanas D, Fan Z, Ang KK and Milas L.. Inhibition of DNA-end binding complex formation as a mechanism for celecoxib-induced radioenhancement in human head and neck carcinoma cells. AACR, 2004.
- Liao Z, Raju U, Mason K, Milas L. Cyclo-Oxygenase-2 enzyme and its inhibition in tumor growth and therapy. In: Cancer Drug Discovery and Development. Humana Press Inc, 2005.
|Title:||Effect of EXEL-9844, a Chk1 and Chk2 Inhibitor, on Radiosensitivity of Murine and Human Cancer Cells|
|Funding Source:||Exelixis Inc|
|Title:||Molecular Targeting to overcome Radiation Resistance in Esophageal Adenocarcinoma|
|Funding Source:||Bristol-Myers Squibb|
|Title:||Esophagus Cancer: Biology of Chemoradiation Resistance and Metastatic Progression-Targeting Cancer Cell Clonogens to Improve Response to Combined Modality Therapy (Proj1)|
|Funding Source:||ImClone Systems|
|Title:||Pre-clinical evaluation of a novel combination therapy with Dasatinib (BMS-354825), C225 and radiation in the treatment of human head and neck squamous cell carcinomas|
|Funding Source:||Bristol-Myers Squibb|
|Title:||Extension of Radiotherapy Research - Proj 4: Selective Molecular Targeted Combined Therapy|
|Title:||Pre-clinical evaluation of a combination therapy with cilengitide, an inhibitor of integrins, and radiation in the treatment of human solid cancers|
|Funding Source:||Merck KGaA, Germany|
|Title:||Targeting C-Met signaling to improve tumor response to radiation|
|Funding Source:||EMD Serono Merck, USA|
|Title:||Pre-clinical evaluation of a combination therapy with cilengitide, erbitux and radiation in the treatment of human solid cancers|
|Funding Source:||Merck KGaA, Germany|
|Title:||Pre-clinical study, combining an anti alphaV integrin antibody, abituzumab (EMD525795, DI-17E6), with radiation|
|Funding Source:||Merck KGaA, Germany|