ABSTRACT
Background: Cancer is one of the leading causes of morbidity and mortality in India. Clinical trials are critical for driving innovation in cancer therapy, diagnosis, and prevention. This study aims to depict the evolving landscape of cancer clinical trials in India by analysing the clinical trials registered in Clinical Trial Registry-India (CTRI). Methods: We identified cancer trials registered in CTRI (between 2007 and 2021) using search terms adapted from the cancer types defined by the National Cancer Institute (USA). We then collated and analysed the publicly available information from CTRI (cancer subtypes, type of trial, treatment intent, type of intervention, sponsor type, recruitment countries) and used descriptive statistics to illustrate the overall as well as year-to-year trend. Findings: In total, we identified 1988 cancer trials, the majority of which focused on treating cancer (63%) and rest of the trials aimed at optimising the operational aspects of surgery (19%), mitigating treatment-related toxicity (10.6%), or treating cancer-related symptoms (7.8%). Focusing on trials with the intent of treating cancer, we found that most were investigating solid tumours as opposed to haematological malignancies with the most prominent cancer subtypes being breast cancer (17%), head and neck cancer (9.8%), lung cancer (9.6%), and cervical cancer (6.6%). The number of trials conducted in a given cancer subtype from our analysis overall correlated to the incidence, mortality, and 5-year prevalence of the respective cancer subtype in India; however, head and neck cancer and cervical cancer were underrepresented in trials as compared with the disease burden. The most common type of intervention was investigational drugs. The most common sponsor types were global pharmaceutical industry (26%) and research institution and hospital (26%). Despite a relatively high cancer burden, the availability of cancer trials in the Northeastern states of India was limited. Interpretation: There is a pressing need for clinical cancer research in India to be better aligned with the nation's healthcare needs and disease burden, focusing on prevalent and deadly cancers while ensuring the availability of clinical trials across geographic regions and underserved populations. Funding: Pi Health USA, a fully owned subsidiary of BeiGene Ltd.
ABSTRACT
Liver X receptors (LXRs) alpha and beta are ligand-induced transcription factors that regulate transcription of genes encoding key regulators of cholesterol metabolism and transport, and of lipogenesis. Despite their high similarity, LXRalpha is the functionally dominant LXR isotype in the liver. The function of nuclear proteins can be affected by their sequestration in the nucleoli. Whereas most nuclear receptors are excluded from the nucleolus, some are not. To explore nucleolar exclusion of LXRalpha and LXRbeta, we used cells expressing cyan fluorescent protein (CFP) chimeras with LXRalpha (CFP-LXRalpha) and wild-type and mutant CFP-LXRbeta and marked the nucleolus with anti-fibrillarin antibody. Significantly more CFP-LXRbeta than CFP-LXRalpha in the nucleoli. Mutations in basic-rich sequences in the DNA binding domain caused some exclusion of CFP-LXRbeta from the nucleolus. Moreover, mutations in the activation function-2, an important protein-protein interaction site in all nuclear receptors, resulted in exclusion of CFP-LXRbeta from the nucleolus. These data suggest protein-protein interactions that may regulate nucleolar sequestration of LXRbeta.
