To understand the molecular mechanisms involved in progression and drug resistance in different subtypes of Triple negative breast cancer (TNBC). Current interest is to identify molecular and patho-physiological vulnerabilities unique to cancer cells that can be used to design diseases specific precision medicine and can overcome drug resistance. Main focus is on cancer specific
Triple Negative Breast cancer (TNBC) is a very heterogeneous, aggressive and metastatic subset of breast malignancy with worse prognosis and shortest disease-free survival rate. Pathologically, TNBC is defined by the lack of hormone receptors (estrogen, ER and progesterone, PR), as well as of human epidermal growth factor receptor2 (HER2) expression, however, it can be further classified into 4-6 distinct molecular subtypes. TNBC accounts for 15-25% of total breast cancers cases detected worldwide, however, recent clinical statistics from different regions of India revealed an excessive burden of TNBC among Indian women (up to a 31% mean prevalence) greatest as compared to any other regions of the world. As obvious targets like ER/PR and HER2 are absent in TNBC, standard clinical management relies mainly on chemotherapeutic agents in neoadjuvant setting or post-resection. Due to high proliferation index TNBC are chemo-sensitive and a fraction of patients (30-45%) does attain initial pathological complete response (pCR). However, several of these cases have early relapse (within 2-5 years post-therapy) with distant metastasis. Moreover, a significant number of patients (>50%) either fail to achieve pCR or have progressed disease during the therapy with metastasis. Management of relapsed chemo-resistant TNBC is extremely challenging and overall prognosis of such patients is often very poor due to limited treatment options, as both choice and response to other therapeutic options (targeted/combination-therapy) are often unpredictable at this stage. Our research laboratory is interested in understanding the molecular, epigenetic and secretome determinants in different subtypes of TNBC tumors that contribute towards the drug resistance to first-line clinical drugs in TNBC Patients.
We combine clinically driven sophisticated TNBC cellular and animal model systems together with cutting edge high-throughput screening approaches to answer these questions. These studies are expected to unmask several novel drug resistance mechanisms in specific TNBC subtypes and hence, can provide rationales for specific therapeutic strategies to re-sensitize cancer cells to cytotoxic therapies used in clinic. The ultimate goal of our studies will be to discover TNBC subtype specific precision medicine for Indian patients that can overcome drug resistance and minimize disease relapse, and thus, can improve the patient’s outcome and survival after therapy.
Scientific Assistant 'E'
Rakesh Kumar, Bijesh George, Marcia Campbell, Nandini Verma, Aswathy Paul, Cecília Melo-Alvim, Leonor Ribeiro, Radhakrishna Pillai, Luis da Costa, Mark Moasser
Nandini Verma, Yaron Vinik, Ashish Saroha , Nishanth Ulhas Nair , Eytan Ruppin, Gordon Mills, Thomas Karn, Vinay Dubey, Lohit Khera, Harsha Raj, Flavio Maina and Sima Lev
Sung-Young Shin, Anna-Katharina Müller, Nandini Verma, Sima Lev, and Lan K. Nguyen
Amir Kedan, Nandini Verma, Ashish Saroha, Michal Shreberk-Shaked, Anna Müller, Nishanth Ulhas Nair and Sima Lev