What's New in Stomach Cancer Research?

Important research on stomach cancer (also known as gastric cancer) is being done in many medical centers and other institutions around the world. Scientists are learning more about what causes the disease and how best to prevent, detect, and treat it.

Risk factors

Diet

Research has clearly shown that differences in diet are an important factor in explaining variations in stomach cancer risk around the world. Research in countries with relatively low stomach cancer risk has provided some insight into risk factors. For example, diets high in preserved meats and low in fresh fruits and vegetables have been linked with higher risk.

Helicobacter pylori infection

Helicobacter pylori (H pylori) is a common type of bacteria that has been linked with an increased risk of stomach cancer. Some studies have shown that certain types of H pylori (especially the cagA strains) are more strongly linked to stomach cancer than others. Some inherited traits related to blood groups may also affect whether someone infected with H pylori will develop cancer. Further research is needed to help doctors determine how to use this information to test which people might be at higher risk for developing stomach cancer.

Research has also found that a healthy diet is important for reducing stomach cancer risk for people infected with H pylori.

Chemoprevention

Chemoprevention is the use of natural or man-made chemicals to lower the risk of developing cancer.

Antioxidants

One of the ways cancer might form is by the creation of chemicals inside cells called free radicals. Free radicals can sometimes damage the genes inside cells, which in some cases might lead to cancer.

Antioxidants are a group of nutrients and other chemicals that can destroy free radicals or prevent them from forming. These nutrients include vitamin C, beta-carotene, vitamin E, and the mineral selenium.

Studies that have looked at using dietary supplements to lower stomach cancer risk have had mixed results so far. There is some evidence that antioxidant supplements might reduce the risk of stomach cancer in people with poor nutrition to begin with, but it's not clear if they'd have the same effects in people who eat healthier diets. Further research in this area is needed.

Antibiotics

Some studies have found that treating chronic H pylori infection with antibiotics may help prevent pre-cancerous stomach abnormalities, but more research is needed.

Although not truly chemoprevention, antibiotics may help prevent stomach cancer from recurring (coming back) in some cases. Research has shown that antibiotics may lower the risk that the cancer will come back in another part of the stomach in people who have been treated for early-stage stomach cancer. Unfortunately, stomach cancers are more often found at a later stage in the United States, so it's not clear how useful these results might be here.

Non-steroidal anti-inflammatory drugs (including aspirin)

Some (but not all) studies have found that people who take non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen might have a lower risk of stomach cancer. More research is needed to better define this possible link. In the meantime, doctors generally don't recommend taking these medicines just to try to lower your risk of cancer, because they can cause serious side effects in some people.

Staging

Sentinel lymph node biopsy

In people diagnosed with stomach cancer, it’s important to find out if it has spread to nearby lymph nodes. Doctors are studying whether sentinel lymph node biopsy (SLNB) can help find the spread of stomach cancer. This technique has proved successful in melanoma and breast cancer.

In this procedure, the surgeon injects a blue dye and/or a radioactive tracer substance into the cancer. These travel to the sentinel lymph nodes, the nearby lymph nodes that would be the first site of cancer spread. Once these nodes are found with the help of the dye or tracer, the doctors can remove these lymph nodes and look for cancer. If no cancer is found in these lymph nodes, then the cancer is unlikely to have reached others, and a full lymph node removal might not be needed. If cancer is found in the sentinel lymph node(s), then all the lymph nodes in the area would need to be removed.

This technique has been shown to help find more lymph nodes to remove, and to find lymph nodes that are more likely to contain cancer cells. But it's not yet clear if this technique is ready for widespread use.

Treatment

Surgery

Doctors are constantly working to improve the surgical techniques used to treat stomach cancer. 

For some very early stage stomach cancers, surgery can be done using endoscopy, in which long, thin instruments are passed down the throat to remove the cancer and some layers of the stomach wall (see Surgery for Stomach Cancer). Surgeons are looking for ways to improve this approach. Unfortunately, most stomach cancers in the United States are not found early enough for this type of surgery.

Surgeons are also studying different approaches to removing part or all of the stomach. For example, some surgeons now do these operations laparoscopically, in which long, thin instruments are passed through small cuts in the abdomen to remove the cancer. This can be done with the surgeon holding the instruments directly, or while sitting at a control panel to move robotic arms with instruments on the ends. While laparoscopic surgery usually results in a shorter hospital stay and a quicker recovery, it’s not yet clear how it compares to standard surgery (using a longer abdominal incision) in terms of other results.

Chemotherapy

Many chemotherapy (chemo) drugs can be used to treat stomach cancer, often in combination with each other. Newer chemo drugs are also being studied. For example, S-1 is an oral chemo drug related to 5-FU. This drug is commonly used for stomach cancer in some other parts of the world, but it is not yet available in the United States.

New ways of giving chemo are also being studied. For example, some doctors are looking at infusing chemo directly into the abdomen (intraperitoneal chemotherapy) to see if it might work better with fewer side effects.

Other studies are testing the best ways to combine chemo with other treatments such as radiation therapy, targeted therapy drugs, or immunotherapy.

A good deal of effort is being directed at improving the results of surgery by adding chemo and/or radiation therapy either before or after surgery. Some studies are also looking at benefits of giving chemo during surgery. Several clinical trials are in progress.

Targeted therapy drugs

Chemo drugs affect cells that divide rapidly, which is why they work against cancer cells. But there are other aspects of cancer cells that make them different from normal cells. In recent years, researchers have developed newer targeted drugs to try to exploit these differences. Targeted drugs sometimes work when standard chemo drugs don't. They also tend to have different side effects than chemo drugs.

Drugs that block HER2: Some stomach cancers have too much of the HER2 protein on the surface of their cells, which helps them grow. Drugs that target this protein, such as trastuzumab (Herceptin) and fam-trastuzumab deruxtecan (Enhertu), can be used to help treat these cancers. Many other drugs that target HER2, such as lapatinib (Tykerb), pertuzumab (Perjeta), trastuzumab emtansine (Kadcyla), and margetuximab, are now being studied for use against stomach cancer in clinical trials.

Drugs that block VEGF and its receptors: VEGF is a protein that helps tumors develop new blood vessels, which they need to grow. Drugs that target VEGF (or the VEGF receptors on the surface of cells) can help stop some stomach cancers from growing. Ramucirumab (Cyramza), a drug that blocks VEGF receptors, can be used to treat some advanced stomach cancers. Other targeted drugs that target VEGF receptors, such as apatinib, are also being studied.

Other targeted drugs: Many other drugs that target different parts of cancer cells are now being studied for use against stomach cancer as well.

Research is also looking at combining targeted drugs with chemotherapy or immunotherapy, or with other targeted drugs.

Immunotherapy

Immunotherapy is an approach that uses drugs to help the body's immune system fight the cancer.

In recent years, drugs called immune checkpoint inhibitors have been shown to be helpful in treating many types of cancer. One of these drugs, pembrolizumab (Keytruda) is now approved to treat advanced stomach cancer in some people, typically after other treatments have been tried. Doctors are now studying whether this drug might be helpful earlier in the course of treatment, or if combining it with other drugs might be helpful. Several other checkpoint inhibitors are also being studied for use in stomach cancer.

Other types of immunotherapy are now being tested for use against stomach cancer as well.

For more information on this type of treatment, see Immunotherapy.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Bendell J, Yoon HH. Progressive, locally advanced unresectable, and metastatic esophageal and gastric cancer: Approach to later lines of systemic therapy. UpToDate. 2020. Accessed at https://www.uptodate.com/contents/progressive-locally-advanced-unresectable-and-metastatic-esophageal-and-gastric-cancer-approach-to-later-lines-of-systemic-therapy on July 15, 2020.

Ku GY, Ilson DH. Chapter 72: Cancer of the Stomach. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.

Mansfield PF. Surgical management of invasive gastric cancer. UpToDate. 2020. Accessed at https://www.uptodate.com/contents/surgical-management-of-invasive-gastric-cancer on July 15, 2020.

National Cancer Institute. Physician Data Query (PDQ). Gastric Cancer Prevention. 2020. Accessed at: https://www.cancer.gov/types/stomach/hp/stomach-prevention-pdq on July 15, 2020.

Shah M. Future directions in improving outcomes for patients with gastric and esophageal cancer. Hem Onc Clinics North America. 2017;31:545.

Shida A, Mitsumori N, Nimura H, et al. Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer. World J Gastroenterol. 2016;22:7431-7439.

References

Bendell J, Yoon HH. Progressive, locally advanced unresectable, and metastatic esophageal and gastric cancer: Approach to later lines of systemic therapy. UpToDate. 2020. Accessed at https://www.uptodate.com/contents/progressive-locally-advanced-unresectable-and-metastatic-esophageal-and-gastric-cancer-approach-to-later-lines-of-systemic-therapy on July 15, 2020.

Ku GY, Ilson DH. Chapter 72: Cancer of the Stomach. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.

Mansfield PF. Surgical management of invasive gastric cancer. UpToDate. 2020. Accessed at https://www.uptodate.com/contents/surgical-management-of-invasive-gastric-cancer on July 15, 2020.

National Cancer Institute. Physician Data Query (PDQ). Gastric Cancer Prevention. 2020. Accessed at: https://www.cancer.gov/types/stomach/hp/stomach-prevention-pdq on July 15, 2020.

Shah M. Future directions in improving outcomes for patients with gastric and esophageal cancer. Hem Onc Clinics North America. 2017;31:545.

Shida A, Mitsumori N, Nimura H, et al. Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer. World J Gastroenterol. 2016;22:7431-7439.

Last Revised: January 22, 2021

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