FASN promotes gallbladder cancer progression and reduces cancer cell sensitivity to gemcitabine through PI3K/AKT signaling.

Lipid metabolism plays an important role in the growth and development of tumors. However, the role of lipid metabolism in gallbladder cancer (GBC) has not been clearly clarified. Here, we demonstrated that fatty acid synthase (FASN), a key enzyme in de novo fatty acid biosynthesis, had upregulated expression in GBC samples both at protein and mRNA levels. Analysis of clinical data indicated the association between elevated FASN expression and poorer histology grades. Furthermore, FASN activity impairment through FASN knockdown or treatment with orlistat resulted in the inhibition of cell proliferation and migration, as well as increased sensitivity to gemcitabine. Both FASN knockdown and orlistat treatment induced cell apoptosis. Mechanistically, impairment of FASN activity suppressed the activation of the PI3K/AKT signaling pathway, which led to increased cell apoptosis and sensitivity to gemcitabine. These findings were also validated through nude mouse xenograft models, thus highlighting the potential of targeting FASN as a clinical treatment strategy. Collectively, the present study underscores the crucial role of FASN in the progression of gallbladder cancer via the PI3K/AKT pathway.

Drug resistance and new therapies in gallbladder cancer.

Gallbladder cancer (GBC) is a highly aggressive malignancy, which poses significant challenges for timely diagnosis, resulting in a dismal prognosis. Chemotherapy serves as a primary treatment option in cases where surgery is not feasible. However, the emergence of chemoresistance poses a significant challenge to the effectiveness of chemotherapy, ultimately resulting in a poor prognosis. Despite extensive research on mechanisms of chemotherapeutic resistance in oncology, the underlying mechanisms of chemoresistance in GBC remain poorly understood. In this review, we present the findings from the last decade on the molecular mechanisms of chemotherapeutic resistance in GBC. We hope that these insights may provide novel therapeutic and experimental targets for further investigations into this lethal disease.

Orphan drugs in different countries and development of new drugs to treat biliary tract cancer.

Biliary tract cancer (BTC), which includes cholangiocarcinoma and gallbladder carcinoma, is a rare malignancy. Due to its low incidence, drugs treating these diseases are scarce, so they can be considered orphan drugs. The main treatment choice for BTC is chemotherapy with gemcitabine or cisplatin or combined use of both, but patients fail to significantly benefit from established chemotherapy. Advancements in immunotherapy and targeted therapy will shed light on ways to improve clinical outcomes for patients with BTC. In conjunction, more new drugs will come onto the market. This article compares the conditions for development of orphan drugs in different countries and it describes several types of new drugs that were recently approved to treat BTC.

The immunological characteristics of gallbladder carcinoma and advances in immunotherapy practices.

Gallbladder carcinoma (GBC) is one of the most common malignant tumors in the biliary system, ranking sixth among gastrointestinal malignancies. In addition, the incidence of GBC has recently increased in China. GBC metastasizes early and invades adjacent organs such as the liver, making patients with GBC ineligible for radical surgery and giving them a poor prognosis. What is more, GBC is more inclined to develop chemo-resistance, which requires new strategies for clinical intervention. Cancer immunotherapy has made great advances over the past few years, with improved clinical efficacy against multiple malignancies, including GBC. This review summarizes the immunological characteristics of GBC as well as current advances in immunotherapies for GBC in order to provide new insights into future treatment and prevention of GBC.