As a result, current biliary tract cancer research is focused on precision medicine, or treatments based on specific mutations. Although this is exciting, this approach is not yet applicable to everyone. It does, however, offer a new way to treat certain patients. Read on to learn more. Symptoms of biliary tract cancer and the latest breakthroughs in treatment. Listed below are some of the most common signs and symptoms of biliary tract cancer.
PTGS-2 gene
There are numerous genetic associations between the PTGS-2 gene and biliar tract cancer. In fact, this gene is expressed in nearly all solid tumors, including the biliary tract and gallbladder. In fact, over 100 different putative variants of PTGS2 have been identified. These variants are noncoding but are synonymous and may play a role in cancer development.
These studies show that genetic variants in genes related to inflammation may contribute to a higher risk of biliary stones and biliary tract cancer. In a recent population-based study, researchers in Shanghai, China, looked at 62 SNPs in 22 genes associated with inflammation and biliary stones. Interestingly, several of these variants were associated with biliary stones, gallbladder cancer, and ampulla of Vater cancer, as well as inflammatory cytokines.
The study found an association between PTGS-2 variants and biliary tract cancer in both males and females. This association was significant even among patients without gallstones. Further, the study’s population-based design minimized the risk of misclassifying gallstones in the control group. Despite these limitations, the study is worth considering as it provides a useful foundation for further research.
The study used a population-based design to minimize the risks of selection, misclassification, and survival bias. The study also included case groups with and without cancer. These two groups were compared to each other in order to find out which risk factor had the strongest effect on the risk of biliary stones and biliary tract cancer. These results confirm a previously known association between the PTGS-2 gene and biliary tract cancer.
EGFR/HER2/VEGF pathways
The EGFR/HER2/VEGF pathway is implicated in several cancers. Biliary tract cancers often display an atypical phenotype. These tumors express both the EGFR and HER2 receptors. Activating mutations in these two receptors can lead to cancer development. However, tumors expressing activating mutations were disproportionately lower in EGFR expression.
Several recent studies have identified various mutations in the EGFR/HER2/VEGF pathways. Specifically, the study reported that EGFR expression is higher in intrahepatic cholangiocarcinomas, and HER2 expression is higher in the extrahepatic biliary tract cancer subtype. Mutations in the HER2 gene have also been reported.
In one study, Werneburg et al. found that bile acid activation of EGFR is accompanied by a role for TGF-a. These results suggest that pathological upregulation of the EGFR gene is responsible for tumorigenesis. Similarly, immunohistochemistry was performed on 49 BTC patient samples for EGFR expression.
EGFR/HER2/VEGF pathway investigation is essential to guide clinical trials. Several selective EGFR inhibitors are now available. These include Gefitinib, Erlotinib, Panitumumab, and Cetuximab. However, the effectiveness of these drugs in BTC remains to be determined. These trials are still preliminary, so further exploration is needed.
Because patients with biliary tract cancer typically have a poor prognosis, chemotherapy is usually given to them in combination with other agents. Currently, combination chemotherapy is the standard of care for this patient group, although second-line treatment is still debatable in the scientific community. The ABC-06 trial, however, provided some slight evidence for the use of mFOLFOX in combination with active symptom control.
COX-2 antiapoptotic action
Research on the role of COX-2 in biliary tract cancer suggests that it contributes to tumor progression by increasing the number of mutated cells in the biliary tract. The mechanism behind COX-2’s involvement in promoting cancer development has yet to be fully understood. But researchers do know that COX-2 inhibits programmed cell death and is implicated in tumor progression. Furthermore, it affects the efficacy of anticancer treatments.
There are three types of COXs. One type, COX-2, is inducible and regulates various inflammatory pathways. COX-2 is regulated by a gene located on chromosome 1. It has been found that COX-2 has 60% homology with COX-1, and the three isoforms have distinct functions. However, they all regulate apoptosis and cell proliferation.
A cancer that involves the bile duct is known as cholangiocarcinoma. This aggressive cancer originates from the epithelial cells of the bile ducts. It is the second most common primary hepatic malignancy after liver cancer, and its incidence is highest in eastern Asia. Patients with a history of liver fluke infection or prolonged biliary inflammation are at high risk of developing CCA.
In addition to inhibiting the growth of biliary tract cancer, COX-2 also inhibits the proliferation of tumor cells. In a study with HT-29 cancer cells, SC-236 inhibited the growth of the cancer cells, with its effect being pronounced when combined with an amphiregulin neutralizing antibody. Furthermore, the inhibition of cell proliferation was found to be associated with an increase in the expression of amphiregulin.
Symptoms
The bile ducts connect the liver and the small intestine, and the cancer in these ducts can occur anywhere along this tract. The ducts transport bile from the liver to the small intestine, and many early tumors do not show any symptoms during a routine physical examination. Because of this, early detection of biliary tract cancer is rare. However, there are some symptoms to look for, and they can indicate bile duct cancer.
Symptoms of bile duct cancer include jaundice, which is a yellowing of the skin and eyes. The liver cannot properly excrete bile if the duct becomes blocked. The bile duct consists of several segments, and a blockage of any of these strands can lead to a yellowing of the skin, whites of the eyes, and urine.
Some common symptoms of biliary tract cancer include abdominal pain, malaise, fatigue, jaundice, and fever. If any of these symptoms are present in your body, it is important to visit a doctor as soon as possible. A doctor will ask questions to find the underlying cause of your symptoms. Once a diagnosis is made, treatment can begin. In many cases, bile duct cancer is not curable, but early detection is crucial to preventing it from spreading.
The most common biliary tract cancer is gallbladder disease, which accounts for 80 to 90 percent of all autopsy cases. Bile duct cancer, or CCA, is the second most common primary liver cancer and accounts for only 3% of gastrointestinal tumours. According to the American Cancer Society, there will be an estimated 11,980 new cases and 4090 deaths from biliary duct cancer in 2020.
Treatment
Surgical resection is the most common form of treatment for biliary tract cancer, although more radical procedures have been developed. However, radical surgery may result in recurrent disease. Biliary tract cancer is a complex disease with multiple etiologies. Recently, genomic footprint data has called into question the biological similarity between different tumors. Additionally, treatment options vary by site. Adjuvant chemotherapy may be beneficial for patients who undergo surgery.
Advanced biliary tract cancers may be difficult to treat, but aggressive surgery can be curative in early stages. Although surgery is the most effective treatment for primary biliary tract cancer, postoperative recurrence is often associated with poor prognosis. In addition, the use of adjuvant chemotherapy regimens for recurrent disease is controversial. In the BILCAP study, capecitabine was given to patients who underwent biliary resection but failed to respond to chemotherapy alone. The authors concluded that the adjuvant treatment improved survival in recurrent patients. While biliary tract cancer surgery is often considered standard of care in Western countries, it is currently the preferred treatment option in Japan.
The authors of the article have no financial or other relationships with the authors’ respective institutions. However, Dr. Patel has published several articles on biliary tract cancer and the liver fluke, which induces cholangiocarcinoma. His data are published in Br J Cancer. A similar study found that intrahepatic cholangiocarcinoma patients were more likely to survive after receiving chemoradiation.
Surgical resection remains the most effective treatment for biliary cancer, although advanced stages require chemotherapy. However, chemotherapy is only effective if it is used within a specialized protocol. Its adverse effects have been well documented. Further, traditional cytotoxic chemotherapies have failed to be effective. Ultimately, the best way to treat biliary tract cancer is a multidisciplinary approach.