Research Projects

Breast cancer is one of the most common cancers among women in India, and its incidence is increasing. Cardiovascular disease (CVD), which is a leading cause of mortality in the general population globally, and also in India is an important non-cancer risk for death in certain breast cancer survivors. There is a paucity of cardiac morbidity and mortality data among breast cancer survivors in India. Prevention and management of cardiac complications during and after cancer treatment are a major challenge for clinicians managing breast cancer patients. Though a tremendous improvement has happened in cancer chemotherapy, the serious adverse effects associated with the therapy are still a major challenge. However, we are currently unable to predict which patients are at highest risk of cardiotoxicity. Anthracyclines (doxorubicin and epirubicin) have wide interindividual variation in Pharmacokinetics and Pharmacodynamics.. Clinical application of pretreatment pharmacogenetic testing to determine drug response and toxicity is still limited in oncology. Understanding these genetic factors through population pharmacokinetic-pharmacodynamic modelling could allow for more personalized treatment and mitigate the risks of cardiotoxicity in Breast Cancer patients. Our current research will focus on addressing the gaps in understanding how pharmacogenomics contributes to anthracyclines induced cardiotoxicity in Indian breast cancer patients. This study aims to use cardiac biomarkers, cardiac imaging, pharmacogenomics, clinical, and pharmacokinetic data to generate tailored treatment protocols for Indian breast cancer patients, potentially enhancing chemotherapy outcomes and reducing cardiotoxicity. The present study will be carried out in central India, AIIMS, Bhopal. HER2-positive breast cancer patients undergoing Anthracyclines chemotherapy treatment will be enrolled and blood samples will be collected for pharmacogenomics and pharmacokinetic studies. Blood samples will be assessed for genotyping of single nucleotide gene polymorphisms (SNPs) variants (Pharmacogenomics PGx) in drug metabolizing enzymes and transporter genes that may predispose patients to chemotherapy-induced cardiotoxicity. For the samples, where the SNPs will not get identified, Whole Exon Sequencing analysis will be conducted. The plasma drug levels of chemotherapeutic drug (Doxorubicin, Epirubicin) will be measured using Liquid chromatography–mass spectrometry (LC-MS/MS) method to assess for pharmacokinetics, and will develop a population pharmacokinetic-pharmacodynamic (PK-PD) model and a risk stratification tool that combines pharmacogenomic data, cardiac biomarker levels, Cardiac imaging findings, to categorize patients based on their cardiotoxicity risk, enabling personalized dosing regimens and close monitoring for high-risk patients.