Unmasking Gallbladder Cancer
Author: Botheina Ghandour
Overview
Gallbladder cancer is aggressive, with epithelial malignancy arising most commonly from the mucosal
lining of the gallbladder. It is a rare cancer that only affects 2 out of 100,000 people. Furthermore, the
cancer presents a higher incidence rate in northern India, East Asia, and regions in South America
(Cleveland Clinic, 2023). Prognosis is unfortunately poor, with five-year survival rates under 20% in most
populations (American Cancer Society, 2024). Additionally, there are no known preventive measures that
can be taken for Gallbladder cancer (Mayo Clinic, 2024)
Cause/Research
The precise cause of gallbladder cancer remains unknown. However, it is known that the cancer develops
due to mutations in DNA, resulting in unregulated cell growth. Research describing the mechanistic
causes of gallbladder cancer has been historically limited due to its low incidence, lack of early detection,
and underrepresentation in clinical trials. Nonetheless, recent molecular studies have begun to uncover
specific genes associated with this disease. Notably, a comprehensive genomic analysis by Nakamura et
al. (2015) proposed that mutations in cell cycle regulatory genes, including TP53, KRAS, and ERBB2,
may account for the majority of gallbladder cancers.
Diagnosis and Management
Early stages of the cancer rarely cause noticeable symptoms, leading to late diagnoses, contributing to
poor prognosis. Furthermore, gallbladder cancer is frequently incidentally diagnosed in patients
presenting with gallstones or undergoing gallbladder removal, underscoring that the disease often goes
unnoticed. Biopsy provides the only way to confirm a diagnosis (Cleveland Clinic, 2023). Surgical
resection remains the cornerstone of curative treatment and can be used during the early stages of the
cancer.
However, most patients present with unresectable or metastatic disease. For these patients, chemotherapy
and radiation therapy can be used to improve symptoms in lieu of a cure (Cleveland Clinic, 2023).
Furthermore, as previously stated, recent genomic studies have identified genes that are frequently
mutated, providing potential therapeutic targets. These genes include: TP53, KRAS, ERBB2 (HER2),
PIK3CA, and ARID1A (Nakamura et al., 2015). Targeting agents such as HER2-directed therapies and
FGFR inhibitors are currently under research and could provide new avenues of treatment for a select
group of patients (LaPelusa, 2023; American Cancer Society, 2024). Investigating these areas is crucial
for developing treatments tailored to patients who present specific biomarkers, leading to personalized
care.
Outlook
While gallbladder cancer remains associated with a poor prognosis and limited therapeutic arsenal, recent
genomic profiling efforts and investigations in personalized therapy represent some promising
developments (Nakamura et al., 2015). Ongoing clinical trials and growing global interest in rare gastrointestinal malignancies reflect a long-overdue shift in research attention. Though historically
understudied, gallbladder cancer is beginning to receive the scientific focus it warrants, offering cautious
optimism for improved outcomes in the years ahead.
Sources
American Cancer Society. (2024). Gallbladder Cancer. https://www.cancer.org/cancer/gallbladder-cancer
Cleveland Clinic. (2023, March 13). Gallbladder Cancer. Cleveland Clinic.
https://my.clevelandclinic.org/health/diseases/17013-gallbladder-cancer
LaPelusa, M., Heumann, T., Goff, L., & Agarwal, R. (2023). Targeted therapies in advanced biliary tract cancers-a narrative
review. Chinese clinical oncology, 12(2), 14. https://doi.org/10.21037/cco-22-93
Mayo Clinic. (2023, July 31). Gallbladder cancer. Mayo Clinic.
https://www.mayoclinic.org/diseases-conditions/gallbladder-cancer/symptoms-causes/syc-20353370
Nakamura, H., et al. (2015). Genomic characterization of biliary tract cancers identifies driver mutations and potential therapeutic
targets. Nature Genetics, 47(9), 1003–1010. https://doi.org/10.1038/ng.337
