Addition of Everolimus to Standard of Care in Carcinoma Gallbladder

Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. It is also the most aggressive cancer of the biliary tract with the shortest median survival from the time of diagnosis. Currently, radical resection is the most effective strategy to potentially cure GBC. Chemotherapy and radiotherapy have been employed as adjuvant and palliative setting, however, the overall survival is still dismal. This study aim to evaluate the addition of Everolimus in addition to standard of care in gallbladder cancer.

Gallbladder cancer is the most common malignant tumour of the biliary tract. It is also the most aggressive cancer of the biliary tract with the shortest median survival from the time of diagnosis. While the incidence rate of GBC varies widely, it has a unique distribution pattern in some regions, where Chile, India, some other Asian countries, Eastern European, and Latin American countries have reported more cases than the rest of the world every year. The other factors, which associated with chronic inflammation and disease pathogenesis, such as hepatobiliary stones, liver flukes, and Salmonella frequently observed in these areas, also constitute the other high-risk factors of bile tract cancer (BTC) including GBC. Currently, radical resection is the most effective strategy to potentially cure GBC. The non-surgical therapies engaged in patients were primarily composed of chemotherapy and radiotherapy. additional therapeutic strategies including next-generation sequencing (NGS), whole-exome sequencing (WES), RNA-sequencing (RNAseq), and single-cell isolation, as well as characterization that have fundamentally opened a novel view enabled to globally identify genetic and epigenetic features and key molecules as potential therapeutic target. Advanced or unrespectable locally advanced disease has a poor prognosis with limited systemic treatment options. Combination platinum-gemcitabine chemotherapy is an active first-line treatment regimen.in particular, specific target treatment, immune therapy, vaccine therapy, biotherapy and nanoparticles have been intensively developed in preclinical and clinical trials. One of target treatment is Mammalian target of rapamycin (mTOR) inhibitors, as The mTOR signaling pathway has critical roles in mammalian metabolism and physiology. The de-regulated activity of mTOR is involved in many pathophysiological conditions, such as aging, Alzheimer's disease, diabetes, obesity, and cancer. Everolimus is a derivative of rapamycin that selectively inhibits mTORC1 (mammalian target of rapamycin complex 1), a key protein kinase complex which regulates cell growth, proliferation and survival. Activation of mTORC1 is mediated by the phosphatidylinositol 3-kinase (PI3K) pathway through activation of AKT/ PKB and subsequent inhibition of the tuberous sclerosis complex.