Research in CTCR is essentially translational. We focus on research questions asked by clinicians with the aim to provide excellent health care to cancer patients with the help of advanced knowledge and technology on real time-basis. CTCR strictly adheres to all ethical and safety guidelines and confidentiality clauses while dealing with clinical data and tissue samples.
TNBC subtype classification
Translational research from major BC clinics in the west has shown promise to identify personalized TNBC clinical management strategies, very few concerted research efforts exist in India despite the high disease prevalence. Identification of distinct clinico-epidemiolgical and molecular characteristics of TNBCs in Indian women will facilitate the development of clinically implementable decision making algorithms and therapeutic options for better clinical management and hopefully, better long-term outcomes.
PI: Dr. Madhura Kulkarni
Prof. L. S. Shashidhara
YAP signature in HER2+ and Triple Negative Breast Cancer
Recent work on limited number of patient samples (Kulkarni et al 2018) indicates that elevated YAP expression strongly co-relates with disease recurrence and shortened survival in breast cancer patients. The study established an association of YAP overexpression with increased metastatic phenotypes in breast cancer cell lines as well as in tumor samples. This co-relation is significant for HER2+ and TNBC subtypes. Furhter investigations with larger cohort of patient samples can prove prognostic potential of YAP signature to identify metastatic subset of HER2+ and TNBC tumors at early stage.
PI: Dr. Madhura Kulkarni
Epidemeology of TNBC subtypes
We are building a database of breast cancer cases in association a with biobank of patient derived tissue materials that will be used for molecular subtyping of TNBC cases. This database is being created with a custom-made data entry portal. The database covers all aspects of patient treatment and outcomes from patient demographics, chemotherapy and surgery details to 3- 5 years of follow-up. This methodology will be carried over to other cancer centers to create a comprehensive dataset that will be initially used to understand the epidemiology and distribution of known TNBC subtypes.
PI: Dr. Devaki A. Kelkar
Profile of Germline Mutations in TNBC
NCCN guidelines recommend germline mutation profiling in hereditary breast and ovarian cancer (HBOC) associated genes in TNBC patients (< 60 years). While comprehensive studies in western populations have now characterized the TNBC germline mutations profile, data from Indian patients is inadequate. Our aim is to establish baseline frequencies of germline BRCA1 mutations in HBOC-associated genes in Indian TNBC using a multi-gene, exome-NGS approach. Further, we aim to establish correlations between such mutational profiles, family history and clinico-pathological characteristics of TNBC in Indian patients.
PI: Dr. Santosh Dixit
Profile of Somatic Mutations in TNBC
Clinical management of TNBCs is challenging due to its aggressive biology , higher mortality and paucity of genomic data till date. Hence, deeper understanding of molecular profile of TNBCs tumors in the Indian cohort is needed. Therefore, we aim to establish a somatic mutation profile in TNBC tumors from Indian patients to identify actionable mutations that can facilitate rationale decision making for targeted chemotherapy.
PI: Dr. Santosh Dixit
Dr. Madhura Kulkarni
Oncoplastic Breast Surgery Techniques
Oncoplastic Breast Surgery incorporates the use of Plastic Surgery tools with oncological surgical practices. Dr. Koppiker is a pioneer in the practice of Oncoplastic Surgery in India. Innovative techniques are used to extend and adapt oncological techniques to the specific needs and financial constraints of of Indian patients. Oncoplastic techniques have been extended for patients with large breasts and large (> 5 cm) and/or multi centric multi focal tumours. Conventionally such patients would be recommended a mastectomy however such an extreme oncoplasty technique has yielded excellent oncological and cosmetic results. Patients with small breasts are conventionally recommended an implant of Acellular Dermal Matrix. Such a matrix is financially prohibitive for many patients. ALDS (Autologous Lower Dermal Sling) technique has been used to cover the tissue expander/implant used in breast reconstruction. Such techniques allow for lower rates of radiation therapy induced complications.
PI: Dr. C.B. Koppiker
Novel Polymer-coated Silicone Implants for Breast Reconstruction Surgery
Oncoplastic Breast Surgery is a recent technique used in BC management that involves Immediate Breast Reconstruction Surgery (IBRS). IBRS refers to the surgical restoration of the breast shape and size with the help Breast Prosthesis (also called as Implant reconstruction) as soon as the diseased breast is removed. However, commercially available silicone breast implants present clinical problems in 15-20 % cases post-IBRS. These problems are manifested as the formation of a constrictive fibrotic capsule post-implantation, known as capsular contracture, which results in firmness, deformity and pain in early stages, ultimately leading to device failure and implant-removal surgery. We are researching the development polymer-coated breast implants. Such novel implants are expected to mitigate radiation induced fibrosis in the breast tissue surrounding the breast implants.
PI: Dr. C.B. Koppiker
Dr. Mayurika Lahiri
Growth control in development and its aberration in cancer
Elaborate network of signalling pathways ensure growth control during animal development such that various organs and tissues attain specific size and shape. Same pathways function in stem cells during tissue regeneration and would healing. Disturbance in any component of this intricate growth control mechanism in human would result in cancer and many ageing-related disorders. Prof. Shashidhara's group have been working on growth control during development for the past 2 decades and have identified key regulators of growth during epithelial tissue morphogenesis using the fruitfly, Drosophila melanogaster. Human orthologues of many of those players are implicated in aggressive tumors and metastasis. Our current efforts are to validate these growth regulators as potential diagnostic and prognostic markers for clinical applications.
PI: Prof. L. S. Shashidhra
In-vitro models of clinical findings
Dr. Lahiri's group has been trying to dissect out the process by which DNA damage or lipid mediators in the micro-environment can lead to cellular transformation of breast epithelial cells using three-dimensional breast acini as a model system. They have identified certain key signalling molecules that get deregulated early on leading to a transformed phenotype and thereby tumorigenic. Currently, her group is using human clinical samples to validate some of their important regulators to understand the molecular signature in Indian breast cancer patients. Tumour derived cell lines are long used for studying the biological processes like metastasis and discovering and evaluating the efficacy of anticancer therapeutics. We would like to establish in vitro (2-D cell cultures, 3-D spheroids) cultures using TNBC cell lines representing various clinical subtypes as they will recapitulate the genomic aberrations observed in primary tumours and allow experimentation by introducing perturbations in the signaling pathways. We would also like to develop organoid cultures using TNBC tumors isolated from patients as these models can be used in studies aimed at understanding the biology of TNBC progression, role of tumor micro-environment and TNBC-specific anti-cancer drug screening.
PI: Dr. Mayurika Lahiri
Clinical and Laboratory Facilities