UK researchers have recently launched a new clinical trial to develop a breath test that could help detect multiple cancer types. This technology could help doctors detect and diagnose cancers earlier by measuring volatile organic compounds (VOCs) through breath biopsy. Depending on conditions, cells can release different patterns of VOCs, and this trial sets out to evaluate if this tool can differentiate between patients with and without various cancer types.This trial will start off with patients with esophageal and stomach cancer and then expand to more cancer types, and is estimated to complete in December 2021.
Taiho Oncology announced that the FDA has granted priority review for the supplemental New Drug Application (sNDA) for LONSURF as new treatment for patients with previously treated advanced or metastatic gastric adenocarcinoma. The drug trial met its primary goal of prolonged overall survival and secondary endpoint measurements of progression-free survival (PFS) in addition to consistent safety and tolerability. LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidide phosphorylase inhibitor.
Helicobacter pylori, a specific strain of bacteria found more often in East Asian patients may be a risk factor for stomach cancer. Doctors want to identify who is most at risk for cancer carrying out a pilot study that would shape treatment and screening strategies for patients infected with this bacterium. Dr. Nina Salama considers that the global differences in stomach cancer risk can be partly attributed to differences in H. pylori itself. One way that H. pylori varies is in the CogA gene which encodes a toxin that helps the bacterium better attach to cells lining the stomach.
Understanding the mutation in the MUC16 gene may be vital to help predict the outcome of the disease as well as possible treatments available for gastric cancer patients. The MUC16 mutation is thought to increase cancer cell’s susceptibility to immunotherapies. Although the genetics of gastric cancer varies greatly from person to person, mutations in the MUC16 gene are very common in gastric cancer as well as other types of cancer. Researchers at Wake Forest University analyzed this mutation and found that MUC16 mutations affects 38.4% of stomach cancer. Moreover, samples containing MUC16 were 1.87 times more likely to have additional mutations. However, patients with the MUC16 mutation lived longer than those with the unaltered gene with a 39% increase in survival. The researchers believe that the use of therapeutic regimens to abrogate immune inhibition may be beneficial for patients with gastric cancer who have MUC16 mutations.
Epstein-Barr Virus (EBV) is a common virus in the United States, however many people do not show symptoms throughout their lives. Although this virus does not directly cause cancer, infection with this common herpes virus increases risk of some cancers such as lymphomas. Furthermore, an increased risk of other types of cancer, including nasopharyngeal and stomach cancers, has been associated with EBV infections. A new drug was tested on mice which inhibited tumor development, thus it may be useful in treating malignancies in EBV-positive patients. In addition, in treated mice, the drug counteracted the cancer-promoting mechanisms by certain proteins. The drug has potential both as a single agent and in combination with other cancer therapies, such as immune system boosting therapies.
Researchers at Spain’s Universitat Politecnica de Valenicia studied the effects of lycopene in the body. Lycopene is an antioxidant found in several fruits and tomatoes, hence it is also found in ketchup. Researchers found that lycopene is more potent in the sauce rather than the fruits because it has been cooked down thus facilitation absorption in the body. This is relevant because previous studies have shown that the consumption of tomatoes inhibit cell growth which can help to guard off gastric cancer. Furthermore, increasing levels of healthy bacteria in the gut can decrease the risk of gastric cancer. Another recommendation is to eliminate the use of cigarettes as it can double the risk of gastric cancer. Lastly, lowering the consumption of salt is recommended as it can have negative effects to diets.
The RAINBOW study pre-treated patients with the doublet of fluoropyrimidine plus a platinum, and later gave paclitaxel plus or minus ramucirumab. Survival rates for this study increased to more than 2 months. Another second line study, REGARD lead by Charlie Fuchs, consisted of best supportive care plus a placebo or best supportive care plus ramucirumab. Looking at both studies together we can say that ramucirumab plus paclitaxel is fit for patients in the second line treatment given as the mean survival of the RAINBOW study was around 9 months for the combination.
Current research of esophagogastric cancer is heading toward building on the signals of activity seen for immunotherapy. Though phase I and phase II trials have given a mixed results, scientists are looking forward to the results of first line immunotherapy trials some of which involve the claudin protein in the body. This protein is overexpressed in most gastric cancers and it is a gap junction protein. Claudin protein combined with chemotherapy has shown great data for its phase II trials and will soon be undergoing phase III trials given improved overall survival of esophagogastric patients. We now know that VEGF-targeted drugs, HER-2 targeted agents, neoadjuvant chemotherapy and radiation added to surgery all improve outcomes in patients with esophagus and gastroesophageal cancers.
In a recent study, researchers found that MUC16 gene mutations in gastric cancer patients lead to higher mutational loads than patients who do not have these mutations. Furthermore, the researchers also found that MUC16 gene mutations affect the immune system and could in also be used to identify patients who could respond to immunotherapies. Of the samples tested in the study, MUC16 gene mutation samples show to have the highest mutation rates compared to those without MUC16. This phenomenon was attributed to tumor instability which is prevalent in gastric cancer. According to The Cancer Genome Atlas (TCGA) patients with MUC16 mutations survived a median 46.9 months, as compared to 26.7 months for those without. In addition, researchers reported MUC16 mutations appeared to influence expressions of other genes such as cell cycle checkpoints, DNA replication and repair, antiaging processing, and signaling pathways involved in the immune system. Lastly, MUC16 is known to modulate immune response to cancer thus patients with MUC16 mutations could benefit from treatments that boost the immune system.
The FDA recently granted an orphan drug designation to Alteogen Inc.’s ALT-P7 for the treatment of patients with gastric cancer. ALT-P7 is an antibody-drug that utilizes a trastuzumab variant form of antibody. This drug may accelerate the advancement of gastric cancer treatment in the United States. Currently in Korea, this drug is undergoing phase 1 clinical trial for the first time in humans. The phase 1 trial at the moment has an emphasis on the benefits of this drug for breast cancer. However, scientists believe ALT-P7 can be extremely helpful in the treatment of HER-2 overexpressing in gastric cancer.