Integrated Head and Neck Oncology

Head and neck cancer is the sixth most common cancer around the world and the leading form of cancer in the Asian subcontinent. The Integrated Head and Neck Oncology Research Program at MSCTR attempts to address two grand challenges in head and neck oncology;
(a) Can we down-stage oral cancer, (b) Could we reverse treatment resistance in head and neck cancer.

Over two-thirds of the patients with head and neck cancer represents advanced stages III/IV, with an overall survival rate of less than 20%. It has been demonstrated that while the outcome of advanced head and neck cancer in India is about 25% below that of developed nations, the survival outcome of early stage cancer that require single modality treatment is about 80%, which is comparable with that of the developed nations.

The primary focus of our research group is hence to understand oral carcinogenesis and develop affordable strategies for early detection and introduce detours in the carcinogenic process.

About 50% of all head and neck cancers recur after ‘curative intent treatment’. As in majority of solid tumours, once the disease recurs or develops distant metastasis, there are no curative treatment options.

The second focus of our research group is to understand mechanisms of treatment resistance and to develop effective methods for detecting disease relapse and to treat the recurrent and metastatic disease with the ultimate goal of ‘molecular pathway’ based adaptive personalized therapy for patients with head and neck cancer.

In an effort to establish an efficient research program and to enable effective translation of the scientific discoveries for clinical benefit, the research program is integrated with the clinical service of Mazumdar-Shaw Medical Center and has initiated collaborations with national and international institutions that offer complementary expertise.

The program adopts two major approaches to address the clinical challenges:

  • A systems biology approach: exploring the whole genome, transcriptome, methylome and proteome as well as the status of targeted markers in tissues, and body fluids, such as saliva and blood

  • A ′cancer stem cell′ perspective: exploring the role of CSCs in the process of tumorigenesis, field cancerization, drug resistance and metastasis

The major ongoing research programs of the group are:

  • Smart-phone based outreach program for early detection and screening; Imaging based methods for point of care screening
  • Salivary biomarkers for the diagnosis and prognosis of oral cancer
  • Integrated ómics approach to predict treatment outcome prediction in laryngo-pharyngeal cancers
  • Cancer Stem Cells (CSC) in field cancerization and tumorigenesis of oral cancer
  • Role of CSCs in drug resistance with resistant cell lines as a model
  • Efficacy of Pathway based targeted therapy in animal models

People

Dr. M A Kuriakose, MD, FRCS

Dr. Kuriakose is Professor and Director, Surgical Oncology and Chief of the Head and Neck Oncology Program, Mazumdar Shaw Cancer Center, Narayana Health, Bangalore. He is also a professor and the director of head and neck oncology translational research program, Roswell Park Cancer Institute, Buffalo. Previously, he has served as Director, Head and Neck Oncology Translational Research program, New York School of Medicine.
He has been instrumental in establishing collaborations with national and international institutions/universities of complementary expertise to address the various issues with the disease in a co-ordinated, multi-centric manner. He has chaired two international and four national conferences and has successfully carried out several projects in chemoprevention and translational research. His work is published in Oral Oncology, Head and Neck, Journal of Applied genetics, Journal of Cancer Research and Therapeutics, Current Opinion in Otolaryngology and Head & Neck Surgery and Laryngoscope. He has served leadership positions in many national and international organizations including Secretary General of International Academy of Oral Oncology, Chairman of Oral Oncology special interest group of International Association of Oral and Maxillofacial Surgeons, Member of AO Research Review Commission, member of steering committee of HPV-AHEAD study of International Agency for Research in Cancer (WHO), secretary of Head and Neck Oncology Cooperative Research Group of India and Secretary of the Foundation of Head and Neck Oncology of India.

Dr. Amritha Suresh, Ph.D.
Principal Scientist
amritha.suresh@ms-mf.org

Dr. Amritha Suresh is a Principal Scientist of the Integrated Head and Neck Oncology Program, at Mazumdar Shaw Center for Translational Research (MSCTR), Narayana Health, Bangalore. She is also a faculty of the Roswell Park-Mazumdar Shaw Cancer Center collaborative Research program. Dr. Suresh completed her doctoral program from Center for Cellular and Molecular Biology (JNU) and served as a Research Associate at Head and Neck Institute, Amrita Institute of Medical Sciences and Research Center, Kochi during which period she was involved in setting up the research facility and the establishment of a Head and Neck tissue repository at the center. She is the recipient of the Young Investigator grant from DBT apart from other grants from DBT and ICMR. She is a member of the Head and Neck Cooperative group of India, a consortium involved in collaborative projects in head and neck cancer and member of executive committee of Foundation of Head and Neck Oncology of India. She has presented in multiple national and international conferences and has published in journals such as Translational Oncology, Head & Neck, Genomics, Oral Oncology and Genome Research.

Bonney Lee James (MSc, MTech Genetic Engineering)
Junior Research Fellow

Project: A Low-Cost Simple Oral Cancer Screening Device for Low-Resource Setting (NIH-DBT Joint funding). The project involves early cancer detection studies which includes imaging by Optical coherence Tomography (OCT) to detect potentially malignant lesion and differentiating it from benign and variations of normal mucosa.  Also working towards developing molecular marker based intra-operative assay system for diagnosing nodal metastasis in head and neck squamous cell carcinoma.

Sumsum Sunny (BDS, MDS, Oral Medicine and Radiology)
DBT-Wellcome Trust Research Trainee
sumsum.sunny@ms-mf.org

Project: Molecular cytology of oral potentially malignant and malignant lesions”Although several novel optical imaging technologies have been introduced for early detection of oral neoplastic lesions, ultimately it requires histopathologic confirmation. Cytology has the potential to develop as oral cancer screening method, with proven efficacy when used pap-smear test in cervical cancer screening program. The proposed project focuses on developing a minimally invasive, marker based cytology method for the detection of potentially malignant and malignant lesions.

Älso involved in piloting early detection research programs – 1) Oncogrid-mobile based early detection (NIH), 2)Cellscope as a telemicroscopic tool (Siemens) 3)Optical Coherence Tomography- Optical diagnostic imaging tool in low resource settings(NIH-DBT) and 4) Fluorescent Imaging- Point of care in-vivo cancer imaging (Vista Dental).

N Reddy Harsha Vardhan(MSc MTech, Genetic Engineering)
Senior Research Fellow
harsha.vardhan@ms-mf.org

Project: Program Support in Head and Neck Oncology (DBT, Govt of India). The study aims to address a major need for developing integrated, pathway based approach to determine treatment resistance/response for laryngo-pharyngeal cancer, which is one of the major cancers in India. An integrated approach to explore the genome, transcriptome and proteome of tissues and the body fluids is the strategy employed in the project. Also working on the “Detection of Metastasis in early stage cancer patients based on Circulating tumour cell profile” that involves enumeration/characterization of Circulating Tumor Cells (CTCs) at a cellular/molecular level, their correlation with prognosis, as an initial step towards identifying potential markers that can enable their clinical application.

Gangotri Siddappa(MSc, Genetics)
Senior Research Fellow (SRF)
gangotri.siddappa@ms-mf.org

Project: ‘Role of Tumor-Initiating Cells (TICs) (stem cell-like cells) in the progression of Oral Squamous Cell Carcinoma (OSCC)’ (Partly funded by Scientific and Engineering Research Board, Government of India). The project involves the discovery of Cancer-Initiating Cell (CIC) markers that may be involved during oral carcinogenesis. It also involves assessing CIC-cancer-associated fibroblasts (CAFs)cross talk in chemopreventive resistance.

M.V Ram Bhupal Reddy (MSc MTech, Genetic Engineering)
Senior Research Fellow (SRF, ICMR fellowship)
PhD scholar, Vellore Institute of Technology (VIT), Vellore
rambhupal.reddy@ms-mf.org

Project: ‘Molecular profile specifying resistance/response to cytotoxic andtargeted chemotherapy in Head and Neck cancer’. The main aim of the study is to identifymarkers/pathway that   can   predict   response/resistance   to   a   specific   treatment, using the meta-analysis approach, and evaluate their efficacy to   improvedisease outcome in head and neck cancer using in vitro and in vivo models. The study attempts to be a step towards the development of personalizedtherapy approach in HNSCC.

Priya Sivadas (MSc Biotechnology)
PhD Scholar, Rajiv Gandhi University of Health Sciences
priya.sivadas@ms-mf.org

Project: Salivary Transcriptome and Proteome for Diagnosis and Prognosis of Oral Cancer (Department of Biotechnology, Govt of India).  The project aims at identification and validation of the potential biomarker candidates in human saliva for the early detection and prognostication of oral squamous cell carcinoma (OSCC) as a step towards development of point-of care assay systems. The study involves proteomic profiling by   Massspectrometry and subsequent validation by ELISA   and   Real-time   PCR.

Ravindra D R (BMLT)
Project Assistant
ravindra.ravidr@ms-mf.org

Project: Head and Neck Biorepository Program which involves preparation and cataloguing of FFPE specimen from the patients. Also involved in carrying out marker profiling for the different projects ongoing in the group with expertise in immunohistochemistry, immuno-flourescence, immunocytochemistry and Florescent-in-situ hybridization (FISH).

Safeena Kulsum(MSc, MTech Biotechnology)
Senior Research Fellow
safeena.kulsum@ms-mf.org

Project: “Molecular signatures specifying cancer stem-like cells from oral squamous cell carcinoma and their relevance in chemo resistance” (RGYI Grant, Department of Biotechnology, Govt of India).  Project involves in re-visiting the concept of oral Cancer stem cells (CSCs) in drug resistance/ treatment failure and whether the drug-resistance CSC-markers can be explored for application in a clinical format. In addition, the strategy of targeting the CSC-fibroblast niche towards reversal of metastasis and chemo resistance in Head and Neck squamous cell carcinoma is also being investigated.

Sudheendra HV(M.Sc Biotechnology)
Senior Research Fellow (SRF)
hv.sudheendra@ms-mf.org

The current project working on is titled “TRAIL & its receptorsin chemotherapy resistant Head & Neck Cancer & possible therapeutic strategies”. The main objective of this project is to profile TRAIL and its receptor expression in chemotherapy resistant HNSCC, correlate expression of DR4 and DR5 with CSC like cells and explore possibility oftargeting these cells by TRAIL mediated therapy. Also involved in validation of salivary proteomic profile and in providing protein-profiling based support for other ongoing projects.

Simple Mohanta (M.Sc Biotechnology)
DST Women Scientist

Project: “Role of Tumor-Initiating Cells in the Development of FieldCancerization in Oral Carcinogenesis”, (Department of Science and Technology, WOS-A scheme). The project aims at mapping of the field of cancerization in terms of the presence of tumor initiating cells and involves correlating the pre-malignant changes occurring in the tumor adjacent normal area with the CSC specific expression profile and subsequently evaluating its prognostic relevance in terms of recurrence and second primary tumor.

Sujatha Darsi (MSc, Biochemistry)
Project Assistant

Project: Program Support in Head and Neck Oncology (DBT, Govt of India), HPV in oral cancer (HNCOG). The projects are multi-centric and involved in co-ordination in terms of patient recruitment, clinical cataloguing and compilation of follow up details in terms of treatment response, recurrence and overall survival.

Alumni

Publications

  • Govindan SV, Kulsum S, Ramanan S, Das D, Seshadri M, Hicks Jr W, Kuriakose MA, Suresh A Establishment and characterization of triple drug resistant head and neck squamous cell carcinoma cell lines. MMR 2014 (Accepted)
  • Baeten J, Suresh A, Johnson A, Kuriakose MA, Flynn A and Kademani D Molecular imaging of oral premalignant and malignant lesions using fluorescently labeled lectins. Translational Oncology 2014 (Accepted)
  • Kekatpure VD, Singh M, Selvam S, Shetkar G, Hedne NC, Trivedi NP, Siddappa G, Govindan SV, Suresh A, Rangarajan B, Dannenberg AJ, Kuriakose MA. Factors Predicting Outcome Following Salvage Treatment for Stage IV Oral Squamous Cell Carcinoma: Evidence of the Potential Importance of the COX-2-Prostaglandin E2 Pathway. Head Neck. 2014 Apr 25. doi: 10.1002/hed.23721
  • Elango JK, Suresh A, Elango EM, Lakshmi S, Hiran KR, Sundaram K, Kuriakose MA. Role of Human Papilloma Virus in Oral Tongue Squamous Cell Carcinoma. As Pac J Can prev 2011; 12(4):889-96.
  • Elango JK, Anandkrishnan N, Suresh A, Iyer SK, Sundaram K R, Kuriakose MA Mouth Self-Examination to improve oral cancer awareness and early detection in a high-risk population Oral Oncol. 2011 Jul; 47(7):620-4. Epub 2011 Jun 8.
  • Suresh A, Vannan M, Dhanya K, Priya S, Elango EM, Thangaraj K and Kuriakose MA. Resistance Response Molecular Signature for Oral Tongue Squamous Cell Carcinoma Disease markers 31 (2011) 1-14
  • Vallinayagam S, Jehan Z, Pradhan S, Hemakumar R, Suresh A, Sridevi R, Ahuja YR, Singh L and Rachel AJ. Novel non-coding RNA from human Y distal heterochromatic block (Yq12) generates testis-specific chimeric Cdc2L2. Genome Research, 2007; 17 (4):433-40.
  • Suresh A, Shah V, Rani DS, Singh BN, UmaPrasad G, Subramanian S, Kumar S and Singh L. A mouse gene encoding a novel member of the WD family of proteins is highly conserved and predominantly expressed in the testis (Wdr13). Molecular Reproduction and Development 72 (2005) 299-310.
  • Singh BN, Suresh A, UmaPrasad G, Subramanian S, Sultana M, Goel S, Kumar S, and Singh L. A highly conserved human gene encoding a novel member of WD-repeat family of proteins (WDR13). Genomics 81 (2003) 315–328.
  • Kekatpure VD, Singh M, Selvam S, Shetkar G, Hedne NC, Trivedi NP, Siddappa G, G SV, Suresh A, Rangarajan B, Dannenberg AJ, Kuriakose MA. Factors predicting outcome following salvage treatment for stage IV oral squamous cell carcinoma: Evidence of the potential importance of the COX-2-prostaglandin E (2) pathway. Head Neck. 2014 Apr 25. doi: 10.1002/hed.23721. Epub ahead of print
  • Folaron M, Kalmuk J, Lockwood J, Frangou C, Vokes J, Turowski SG, Merzianu M, Rigual NR, Sullivan-Nasca M, Kuriakose MA, Hicks WL Jr, Singh AK, Seshadri M. Vascular priming enhances chemotherapeutic efficacy against head and neck cancer. Oral Oncol. 2013 Sep; 49(9):893-902. doi: 10.1016/j.oraloncology.2013.06.011. Epub 2013 Jul 23.
  • Battoo AJ, Thankappan K, Ahmad SZ, Hedne N, Balasubramanian D, Trivedi N, Iyer S, Kuriakose MA. Efficacy of per oral access in the surgical management of T2/T3 oral cavity squamous cell carcinoma. Otolaryngol Head Neck Surg. 2012 Dec; 147(6):1069-75. doi: 10.1177/0194599812456812. Epub 2012 Aug 7.
  • Suresh A, Vannan M, Kumaran D, Gümüs ZH, Sivadas P, Murugaian EE, Kekatpure V, Iyer S, Thangaraj K, Kuriakose MA. Resistance/response molecular signature for oral tongue squamous cell carcinoma. Dis Markers. 2012; 32(1):51-64. doi: 10.3233/DMA-2012-0860.
  • Elango KJ, Suresh A, Erode EM, Subhadradevi L, Ravindran HK, Iyer SK, Iyer SK, Kuriakose MA. Role of human papilloma virus in oral tongue squamous cell carcinoma. Asian Pac J Cancer Prev. 2011; 12(4):889-96.
  • Elango KJ, Anandkrishnan N, Suresh A, Iyer SK, Ramaiyer SK, Kuriakose MA. Mouth self-examination to improve oral cancer awareness and early detection in a high-risk population. Oral Oncol. 2011 Jul; 47(7):620-4. doi: 10.1016/j.oraloncology.2011.05.001. Epub 2011 Jun 8.
  • Trivedi NP, Ravindran HK, Sundram S, Iyer S, Kekatpure V, Durah S, Kuriakose MA. Pathologic evaluation of sentinel lymph nodes in oral squamous cell carcinoma. Head Neck. 2010 Nov; 32(11):1437-43. doi: 10.1002/hed.21345.
  • Kekatpure VD, Trivedi NP, Shetkar G, Manjula BV, Mathan Mohan A, Kuriakose MA. Single perforator based anterolateral thigh flap for reconstruction of large composite defects of oral cavity. Oral Oncol. 2011 Jun; 47(6):517-21. doi: 10.1016/j.oraloncology.2011.03.023. Epub 2011 Apr 12.
  • Cancer stem cell mediated acquired chemoresistance in head and neck cancer can be abrogated by aldehyde dehydrogenase 1 A1 inhibition. Kulsum S, Sudheendra HV, Pandian R, Ravindra DR, Siddappa G, R N, Chevour P, Ramachandran B, Sagar M, Jayaprakash A, Mehta A, Kekatpure V, Hedne N, Kuriakose MA, Suresh A. MolCarcinog. 2016 Jul 6. doi: 10.1002/mc.22526.
  • A Minimal DNA Methylation Signature in Oral Tongue Squamous Cell Carcinoma Links Altered Methylation with Tumor Attributes. Krishnan NM, Dhas K, Nair J, Palve V, Bagwan J, Siddappa G, Suresh A, Kekatpure VD, Kuriakose MA, Panda B. Mol Cancer Res. 2016 Sep;14(9):805-19. doi: 10.1158/1541-7786.MCR-15-0395.
  • A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia. Kuriakose MA, Ramdas K, Dey B, Iyer S, Rajan G, Elango KK, Suresh A, Ravindran D, Kumar RR, R P, Ramachandran S, Kumar NA, Thomas G, Somanathan T, Ravindran HK, Ranganathan K, Katakam SB, Parashuram S, Jayaprakash V, Pillai MR. Cancer Prev Res (Phila). 2016 Aug;9(8):683-91. doi: 10.1158/1940-6207.CAPR-15-0390.
  • Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients.Kekatpure VD, Bs N, Wang H, Zhou XK, Kandasamy C, Sunny SP, Suresh A, Milne GL, Kuriakose MA, Dannenberg AJ. Cancer Prev Res (Phila). 2016 Jun;9(6):428-36. doi: 10.1158/1940-6207.CAPR-15-0412.
  • Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence. Krishnan N, Gupta S, Palve V, Varghese L, Pattnaik S, Jain P, Khyriem C, Hariharan A, Dhas K, Nair J, Pareek M, Prasad V, Siddappa G, Suresh A, Kekatpure V, Kuriakose M, Panda B.F1000Res. 2015 Nov 5;4:1215. doi: 10.12688/f1000research.7302.1.
  • Mobile health application for remote oral cancer surveillance.Birur PN, Sunny SP, Jena S, Kandasarma U, Raghavan S, Ramaswamy B, Shanmugam SP, Patrick S, Kuriakose R, Mallaiah J, Suresh A, Chigurupati R, Desai R, Kuriakose MA. J Am Dent Assoc. 2015 Dec;146(12):886-94. doi: 10.1016/j.adaj.2015.05.020.
  • Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer. Reddy RB, Bhat AR, James BL, Govindan SV, Mathew R, Ravindra DR, Hedne N, Illiayaraja J, Kekatpure V, Khora SS, Hicks W, Tata P, Kuriakose MA, Suresh A. PLoS One. 2016 Jan 25;11(1):e0147409. doi: 10.1371/journal.pone.0147409. eCollection 2016.
  • Data from human salivary proteome - A resource of potential biomarkers for oral cancer.Sivadasan P, Kumar Gupta M, Sathe GJ, Balakrishnan L, Palit P, Gowda H, Suresh A, Abraham Kuriakose M, Sirdeshmukh R. Data Brief. 2015 Jul 2;4:374-8. doi: 10.1016/j.dib.2015.06.014.
  • Impact of Short-term 1,25-Dihydroxyvitamin D3 on the Chemopreventive Efficacy of Erlotinib against Oral Cancer.Bothwell KD, Shaurova T, Merzianu M, Suresh A, Kuriakose MA, Johnson CS, Hershberger PA, Seshadri M. Cancer Prev Res (Phila). 2015 Sep;8(9):765-76. doi: 10.1158/1940-6207.CAPR-14-0454.
  • Human salivary proteome--a resource of potential biomarkers for oral cancer.Sivadasan P, Gupta MK, Sathe GJ, Balakrishnan L, Palit P, Gowda H, Suresh A, Kuriakose MA, Sirdeshmukh R. J Proteomics. 2015 Sep 8;127(Pt A):89-95. doi: 10.1016/j.jprot.2015.05.039.
  • Establishment and characterization of triple drug resistant head and neck squamous cell carcinoma cell lines.Govindan SV, Kulsum S, Pandian RS, Das D, Seshadri M, Hicks W Jr, Kuriakose MA, Suresh A. Mol Med Rep. 2015 Aug;12(2):3025-32. doi: 10.3892/mmr.2015.3768.
  • Cancer stem cells and field cancerization of oral squamous cell carcinoma. Simple M, Suresh A, Das D, Kuriakose MA. Oral Oncol. 2015 Jul;51(7):643-51. doi: 10.1016/j.oraloncology.2015.04.006. Review.
  • Molecular imaging of oral premalignant and malignant lesions using fluorescently labeled lectins.Baeten J, Suresh A, Johnson A, Patel K, Kuriakose M, Flynn A, Kademani D. TranslOncol. 2014 Apr;7(2):213-20. doi: 10.1016/j.tranon.2014.02.006.
  • Factors predicting outcome after salvage treatment for stage IV oral squamous cell carcinoma: Evidence of the potential importance of the cyclooxygenase-2-prostaglandin E2 pathway.Kekatpure VD, Singh M, Selvam S, Shetkar G, Hedne NC, Trivedi NP, Siddappa G, Govindan SV, Suresh A, Rangarajan B, Dannenberg AJ, Kuriakose MA. Head Neck. 2015 Aug;37(8):1142-9. doi: 10.1002/hed.23721.