Gallbladder cancer is a rare type of tumor, but as in the case of sarcoma, regardless of the rarer tumors, Cancer Degree also feels it is very necessary to sort out the basic treatment strategies for this disease, and whether it is necessary to do genetic testing in the concept of precision medicine, to guide the subsequent targeted drugs, and whether it is worthwhile to try the cross-cancer drug use? Are there any new studies proving the effectiveness of certain existing targeted drugs? Overview of gallbladder cancer Gallbladder cancer is formed when certain cells of the gallbladder undergo a genetic mutation, lose their normal growth regulation and become malignant proliferating cancer cells. Gallbladder cancer is a relatively rare type of tumor. The gallbladder is a pear-shaped organ located in the upper abdomen underneath the liver. The gallbladder stores bile made from the liver, which is used to digest fats. As food is broken down in the stomach and intestines, the gallbladder releases bile through a tube called the common bile duct, which connects the gallbladder and liver to the first part of the small intestine and acts as a link. The gallbladder is located in the upper abdomen below the liver and is a green, pear-shaped organ The wall of the gallbladder has three main layers of tissue: the mucous membrane layer (inner layer), the muscular layer (middle layer), and the plasma membrane layer (outer layer). Between these three layers are the supporting nodular hoof tissues. Primary gallbladder cancer originates from the inner layer and gradually spreads and metastasizes to the outer layer as it grows. Generally speaking, women have a higher risk of gallbladder cancer than men. Treatment of Gallbladder Cancer The treatment of gallbladder cancer needs to be considered according to various factors, such as its stage, whether it is primary or recurrent, and the morphology of the cancer cells under microscope, etc. Only when the gallbladder cancer is confined to the primary site and has not metastasized can it be cured by surgery, while the other modes of treatment are conservative treatments, which are aimed at increasing the survival period of the patients and improving the quality of life. Of course, science and technology are developing rapidly, and there may be new technologies and treatments to control the tumor in the next few years, so no matter what, persistence is the hope. At present, the mainstream treatments for gallbladder cancer include surgery, radiotherapy and chemotherapy. Surgery The gallbladder and surrounding tissues, including nearby lymph nodes, can be removed through cholecystectomy. This surgery is usually performed laparoscopically. If the tumor has spread and cannot be removed, then the following procedures may be used to improve quality of life. Surgical biliary bypass, if the growth of the tumor is blocking the flow of bile to the small intestine, then this procedure needs to be performed, where the gallbladder or bile duct is cut and sutured to the small intestine to create a new pathway that bypasses the blocked area. Stent placement, if the tumor is blocking the bile duct, a stent (thin flexible tube) may be placed to allow bile that is blocked in that area to flow out. The stent can be placed in a variety of ways, including externally, around the blocked area to drain bile into the small intestine. Percutaneous hepatic puncture biliary drainage is used as a strategy to unblock bile if stent placement is not possible. to treat obstructive jaundice caused by the tumor. Radiation therapy There are two types of radiation therapy: external radiation therapy and internal radiation therapy. The treatment depends on the type and stage of the tumor. Chemotherapy The drugs, regimens, and forms of chemotherapy drug delivery used in chemotherapy depend on the type and stage of the tumor, and there are generally clear guidelines. The chart below shows some of the major treatments and median survival for biliary tract cancer. (Note: Biliary tract cancers include gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma). Treatment Measures and Median Survival for Biliary Tract Cancer Additionally patients may be able to enroll in certain clinical trials Information on Clinical Trials for Gallbladder Cancer Targeted Therapies for Gallbladder Cancer Now let’s look at the data on targeted therapies for gallbladder cancer for which clinical trials have been completed. As shown below, most of the clinically enrolled patients were non-selective. And most of the clinical data results are less than favorable. Data of some completed clinical trials of targeted therapy for gallbladder cancer Through Figure 5 we can see that for non-selective gallbladder cancer patients, if they go the route of targeted therapy, the highest objective remission rate is Ebitux combined with gemcitabine and oxaliplatin. Ebitux (or panitumumab) in combination with other chemotherapies also has a relatively high objective remission rate, i.e., protein antibodies against EGFR in combination with chemotherapy can achieve a high objective remission rate. Efficacy rates for erlotinib, a small molecule tyrosine kinase inhibitor targeting EGFR, are not very consistent, with the highest being 8%, and the multi-targeted small molecule sorafenib alone has a very embarrassing efficacy rate of 0 in one study and 2% in another, and sunitinib has an efficacy rate of 8.9%. Referring to these data, gallbladder cancer patients who blindly try small molecule targeted drugs need to be a bit cautious. Of course, there are some other targeted drugs that are undergoing corresponding clinical trials, and we will report the corresponding results to you later. Many of the data in Figure 5 are not selected for the enrolled patients, and some studies have shown that the response rate of Her2-targeted drugs will be much higher in patients with Her2 overexpression. Therefore, although gallbladder cancer, which is a rare type of cancer, is not as hot as lung cancer, and there are so many research data, based on the current understanding, it is still worthwhile to consider the selection of targeted drugs for the corresponding gene mutation and protein expression level. and there are indeed clinical trials to study these. Although there are no data reports, we will give you a brief overview of each gene mutation, the targeted drugs that can be used, and their scientific logic. Genetic alterations in cholangiocarcinoma and possible cross-indication drugs If genetic testing or protein expression level testing is performed for cholangiocarcinoma and genetic alterations are found, the corresponding cross-indication drugs are as shown in Fig. 6, with each genetic alteration having its own corresponding drug, and sometimes these drugs need to be used in combination. Currently, no targeted drugs have been approved for gallbladder cancer, and many of the clinical trials that have been conducted have not tested patients for genetic mutations before using the corresponding targeted drugs, so the data are imperfect. However, researchers have begun to conduct similar clinical trials, i.e., recruiting patients based on genetic alterations to observe the efficacy of targeted therapies. This is something to look forward to. We searched a lot of the literature, but still haven’t thoroughly answered that question. That is, whether it is feasible to use genetic testing across indications in gallbladder cancer. Unlike gastric cancer, many clinical trials of targeted therapy for genetic mutations in gastric cancer are negative, so it is not meaningful to do genetic testing, but there is no report on this in gallbladder cancer, and there is no completely negative conclusion, so CancerDo thinks that it is worth to try, and also there are researches showing that with high expression of Her2 and so on, the efficacy rate of the targeted drug is really much better. effective rate is indeed much better. However, genetic alteration of gallbladder cancer should focus on the detection of both gene mutation and protein expression, i.e., the use of sequencing technology to detect possible gene mutation, and the use of immunohistochemistry to detect the expression of proteins such as EGFR, HER2, etc., because the current data show that the combination of chemotherapy with EGFR monoclonal antibody drugs in non-selective populations may obtain a relatively high objective response rate. Only the combination of genetic testing and immunohistochemistry can provide a better understanding of genetic mutations and the selection of targeted drugs.