By Hannah Kerfoot
Gastric (stomach) cancer and oesophageal cancers are not the most common cancers (accounting for only 2% each of all new cancer cases in the UK), however these cancers are classed as being less survivable. Patients with oesophageal cancer have a 10 year survival rate of 12% and patients with gastric cancer have a survival rate of 17%.
Symptoms of oesophageal and gastric cancers
As expected of a disease which affects the digestive system, both of these cancers can have the symptom of weight-loss and dysphagia (difficulty swallowing). Although both cancers occur in the digestive system, the position in which they occur means they present with different symptoms since the cancer acts on different stages of digestion.
For example, ‘higher up’ the digestive system, early oesophageal cancer symptoms of indigestion, heartburn, and pain in the throat, often are confused for symptoms of local inflammation or ulceration.
Meanwhile, with gastric cancer, which is ‘lower down’ the digestive system, symptoms include gastric pain and dyspepsia (indigestion), feeling full after eating little and loss of appetite, feeling or being sick, dark coloured faeces, and tiredness due to anaemia.
Gastric cancer and oesophageal cancer are more common in older people and in men than women. Both cancers can be caused by smoking tobacco.
However, there is a unique link between gastric cancer and a strain of bacteria called Helicobacter pylori (H. pylori).
H. pylori and gastric cancer risk
40% of gastric cancers in the UK are attributable to helicobacter infection.
Mechanism 1: Patient is infected with H.pylori → patient expresses CagA protein → CagA is integrated into cells and becomes pathogenetic by activating signalling cascade (SHP2, Abl or Src kinases)
Mechanism 2: Patient is infected with H.pylori → H.pylori secrete peptidoglycan into patient’s cells → this causes upregulation of pro-inflammatory cytokines (IL-8 and COX) → these pro-inflammatory cytokines cause chronic inflammation and cancer development
Mechanism 3: Patient is infected with H.pylori → H.pylori secretes VacA toxin → patient’s T-cell response suppressed → stomach lesions are formed with little immune response due to suppressed T-cells
Although H.pylori is present in many people’s stomachs, smoking and diet can increase the risk of that infection causing cancer.
Gastro oesophageal reflux disease (GORD) and oesophageal cancer risk
GORD increases the risk of oesophageal cancer. As stomach acid flows back up the oesophagus from the stomach, this can cause damage to the oesophagus. Similar to how stomach ulcers and inflammation increase risk the risk of gastric cancer, the damage done to tissues and subsequent healing gives cells more opportunity for incorrect duplication, mutation and development into cancer.
Developments in the treatment and diagnosis of gastric cancers
There have been positive and encouraging updates to the diagnosis and treatment of gastric cancers. This includes advances to diagnostic methods to determine predictive biomarkers, such as liquid biopsies to assess circulating tumour DNA (ctDNA) for known biomarkers of gastric cancer, including HER2, MSI, MMR, and PD-L1.
Additionally, there have been advances in precision therapy, such as the discovery of the low expression of the CLDN18.2 gene in gastric tumour tissues. This has led to the development and approval of claudin-18.2-targeted antibodies (zolbetuximab).
There are ongoing trials investigating chemotherapy-free neoadjuvant therapy in patients with resectable gastric cancer, like the INFINITY trial (which tested tremelimumab and durvalumab), which if successful, could mean that patients could provide a better neoadjuvant therapy option for patients prior to resection of their gastric cancer.
Another development is the tailoring of neoadjuvant therapies, for example the development of a perioperative fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regime. This treatment is responsible for an increase in the 5-year overall survival from 23% for surgery alone to 45% for AIO-FLOT4 (FLOT-Surgery-FLOT).
Finally, the way that anti-cancer drugs are delivered to the sites in the body has improved; for example antibody-drug conjugates (ADCs) have been developed, such as trastuzumab deruxtecan), which binds to HER-2 receptors. .
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