Gastric (Stomach) Cancer

Gastric cancer is a malignancy that develops in the lining of the stomach. The most common type is adenocarcinoma, which arises from the glandular cells of the stomach mucosa. The stomach can also be the site of gastrointestinal stromal tumors (GISTs), lymphomas, and neuroendocrine tumors — each of which is managed differently from adenocarcinoma.

Gastric adenocarcinoma is now understood to be a molecularly diverse group of cancers, with distinct subtypes — HER2-positive, MSI-H, EBV-associated, and others — that respond differently to specific treatments. Knowing your exact subtype is essential before treatment begins.

Early gastric cancer is often asymptomatic, which is why it is frequently diagnosed at a more advanced stage. When symptoms do appear in early disease, they are typically vague and easily confused with common conditions like gastritis or peptic ulcer disease.

Symptoms that may appear include persistent upper abdominal discomfort, a feeling of fullness after small meals, mild nausea, loss of appetite, and unexplained weight loss. In some cases, occult (hidden) blood loss from the tumor causes iron-deficiency anemia and fatigue before any other symptoms are noticed. Any of these symptoms — particularly when persistent or worsening — should prompt investigation by upper GI endoscopy rather than empirical acid-suppression therapy alone.

Diagnosis requires upper GI endoscopy (EGD) with targeted biopsies of the suspicious area. The biopsy specimen is reviewed by a pathologist to confirm malignancy, determine histologic type and grade, and classify the tumor according to the Lauren system (intestinal, diffuse, or mixed type).

After tissue diagnosis, a staging workup follows — typically including CT scanning of the chest, abdomen, and pelvis, endoscopic ultrasound (EUS) to assess depth of invasion and nodal status, and in some cases a PET scan or diagnostic laparoscopy. For advanced disease, molecular testing — HER2, MSI, PD-L1, CLDN18.2, and NGS — is performed on the tumor sample, as these results directly determine which systemic therapies are appropriate.

HER2 testing determines whether the tumor overexpresses the HER2 protein or has HER2 gene amplification. A result of IHC 3+ or IHC 2+ confirmed by FISH (or ISH) as positive means your tumor is HER2-positive — this opens eligibility for trastuzumab in combination with chemotherapy as first-line treatment for advanced gastric cancer.

HER2-positive gastric cancer also becomes eligible for trastuzumab deruxtecan (T-DXd) after first-line treatment — an antibody-drug conjugate that has shown strong efficacy in this subgroup. An equivocal IHC 2+ result without FISH confirmation should be followed up, as the distinction matters significantly for treatment eligibility. If you are unsure whether FISH testing was done, ask your oncology team or share reports with CancerFax for review.

MSI-H stands for microsatellite instability-high. Microsatellites are short repeated DNA sequences in the genome; when the cellular machinery that repairs DNA copying errors (mismatch repair, or MMR) is deficient, these sequences accumulate errors and the cancer is described as MSI-H or dMMR (deficient mismatch repair).

MSI-H tumors have a high mutational burden and an immune-activated microenvironment. This makes them significantly more responsive to immune checkpoint inhibitors (pembrolizumab, nivolumab) compared to MSS (microsatellite stable) tumors. Identifying MSI-H status changes first-line treatment selection and is one of the reasons comprehensive molecular testing at diagnosis is so important.

Treatment for metastatic gastric cancer is guided by molecular biomarkers. In HER2-positive disease, the standard first-line approach combines trastuzumab with platinum-fluoropyrimidine chemotherapy; pembrolizumab may be added for additional benefit. In HER2-negative disease with high PD-L1 CPS, nivolumab or pembrolizumab in combination with chemotherapy has demonstrated improved outcomes.

For CLDN18.2-positive, HER2-negative patients, zolbetuximab combined with chemotherapy is now an option where approved. MSI-H patients benefit substantially from checkpoint inhibitors. In second line, ramucirumab with paclitaxel, irinotecan-based regimens, or trastuzumab deruxtecan (in HER2-positive patients) are used depending on prior therapy. Access to some of these agents — including T-DXd and zolbetuximab — may require international coordination in regions where they are not yet locally available.

A second opinion is worth seeking at several key points. If your diagnosis involves locally advanced disease and you are unsure whether surgery is the right first step, an experienced upper GI surgical oncologist should weigh in. If your molecular tests — particularly HER2 or MSI — returned equivocal or borderline results, confirmation at a reference laboratory is important before starting treatment.

If you have been diagnosed with diffuse-type gastric cancer, signet ring cell carcinoma, or linitis plastica — more aggressive subtypes with specific management considerations — specialist review adds value. After progression on first-line therapy, a second opinion from an advanced GI oncology specialist can help identify trial options, targeted agents based on NGS findings, or access to newer drugs that may not yet be available at your local center.

Yes — gastric cancer is one of the most active areas of gastrointestinal oncology research globally. Active trial areas include: CAR-T cell therapy targeting CLDN18.2 and other antigens (primarily in China); FGFR2b inhibitors in FGFR2b-amplified tumors; combinations of checkpoint inhibitors with VEGFR inhibitors or anti-CTLA4 agents; HER2-low targeting with new-generation ADCs; and perioperative immunotherapy combinations in resectable disease.

Many of the most advanced gastric cancer trials are running at specialist centers in China, South Korea, Japan, and the US/EU. Identifying trial eligibility requires current NGS results and knowledge of which centers are actively recruiting. CancerFax can assist in reviewing your molecular profile against open trial criteria and provide guidance on centers where enrollment may be possible.

Yes. CancerFax supports gastric cancer patients and families through every stage of the treatment navigation process — starting with a thorough review of biopsy reports, endoscopy findings, HER2 and MSI test results, PD-L1 scoring, and any NGS reports to establish your exact disease subtype and molecular profile.

Based on this review, we identify which standard treatment options apply, whether any advanced therapies — trastuzumab deruxtecan, zolbetuximab, immunotherapy combinations — are relevant for your subtype, and which clinical trial programs (including those in China and South Korea, where many active gastric cancer programs run) may be worth pursuing. We coordinate second opinion consultations with specialist gastric cancer oncologists and assist with documentation, report translation, and center liaison for patients exploring treatment internationally. Send your medical reports to get started.