Current Targeted Therapy in Gallbladder Cancer

Introduction The most frequent malignancy of the biliary tract system, gallbladder cancer (GBC) is among the top six gastrointestinal tract neoplasms globally. For gallbladder cancer in its early stages, surgery is still the recommended course of therapy. Appropriate surgical techniques are chosen to achieve the best surgical outcome based on the anatomical location of the main tumor, precise preoperative staging, and strict control of surgical indications. Nonetheless, the majority of patients were either diagnosed at a locally advanced stage of the disease or it had already metastasized. Even after radical resection for gallbladder cancer, the ۵-year survival rate and postoperative recurrence rate are still inadequate. Therefore, in the whole-course therapeutic management of gallbladder cancer patients, there is an urgent need for more treatment alternatives, such as neoadjuvant therapy, postoperative adjuvant therapy, and first- and second-line therapies of local progression and metastasis. The use of immunotherapy and molecularly targeted medications has expanded treatment options and given patients hope for gallbladder cancer in recent years. This study will provide insight over the targeted therapy trends for gallbladder cancer based on the most recent developments in the field. Methods Using the keywords ((Gallbladder cancer[Title/Abstract]) OR (biliary tract cancer[Title/Abstract])) AND (targeted therapy[Title/Abstract]), a comprehensive search was carried out in the PubMed database between ۲۰۱۸ and ۲۰۲۴. There were ۱۸۰ results shown. Review articles and non-English/unrelated pieces were excluded. Overall, five studies were included. Results Many medications have been developed for targeted treatment, mostly in the form of small molecules and vaccinated antibodies. Therapeutic antibodies specifically bind to cell membrane receptors or their ligands to regulate cell proliferation or apoptosis, while small molecules with molecular weight <۹۰۰ Da can be easily transported into cells to inactivate specific proteins or enzymes, thereby inhibiting tumor cell growth. Certain medications were developed to specifically target extracellular chemicals that either trigger an immune response or facilitate angiogenesis inside the tumor microenvironment. This led to the suppression of metastasis, angiogenesis, and tumor development. Human epidermal growth factor receptor ۲ (HER۲), growth factor receptor tyrosine kinases (RTKs) (EGFR, vascular endothelial growth factor receptor; VEGFR); programmed death receptor ۱ (PD-۱)/programmed death ligand ۱ (PD-L۱), TP۵۳, KIT, CDKN۲A/B, phosphatidylinositol ۳-kinase (PI۳K)/AKT/mammalian target of rapamycin (mTOR), and RAS/BRAF/MEK/MAK are some of the signaling pathways that these targeted therapies can target. Conclusion Patients with advanced GBCs may live longer due to targeted therapies, which have also significantly expanded the pool of available treatment choices for those with refractory diseases. Based on advancements in the diagnosis of genetic changes, the treatment landscape for patients with advanced GBCs remains dynamic in terms of targeted therapy.

کلیدواژه ها:

Gallbladder cancer ، biliary tract cancer ، targeted therapy