Treatment of metastatic and inoperable gastric cancer starts from chemotherapy, as surgery is not able to remove the whole tumor at this stage. Unfortunately, chemotherapy is often accompanied by unpleasant symptoms and fails to be effective in a number of tumor types. Immunotherapy is a newer option that is characterized by better tolerability and efficiency in patients with advanced cancer stages.
Peculiarities of the examination before the targeted and immunotherapy start
Although immunotherapy is performed according to the standardized international protocols, treatment is always chosen after the precise immunohistochemical cancer diagnosis. It reveals oncogenic immunological changes and creates the background for their correction.
The first part of examination is obtaining sample of the tumor. This may be done during gastroscopy or surgery. Cancer cells are processed with hematoxylin and eosin these are staining agents that interact with certain cellular components. In order to improve tissues preservation, a sample can also be fixed with formalin or embedded in the paraffin.
The following immunohistochemical markers are important in patients with stomach cancer:
- HER2 reflects the therapeutic response, prognosis and risks of metastasizing into lymph nodes.
- VEGF reflects the therapeutic response and rate of the tumor progression.
- PD-1, CTLA-4, IDO1, LAG-3 are superficial cellular components that are targeted by immunotherapy.
According to the modern protocols, HER2 test is now mandatory for all patients with stomach malignancies.
Combination of the conventional options with immunotherapy
Immunotherapy may be performed as an independent treatment or in combination with chemo- and radiotherapy. Three modes of it are available now:
- Active immunotherapy.
- Adoptive cell immunotherapy.
- Antibody therapy.
Active immunotherapy influences patients own antineoplastic immunity. For instance, vaccines lower gastric cancer risk, as they reactivate dormant tumor-specific and antigen-specific T-cells. Such therapy does not prolong the overall survival, but improves the prognosis in patients with solid gastric tumors. Other types of active anticancer immunization are cytokine and dendritic cell therapy.
Adoptive cell immunotherapy and antibody therapy work with the humoral component of immune system. It employs cytokines and monoclonal antibodies that attack atypical cells. Lymphocytes that infiltrate a tumor or circulate in the peripheral blood are combined with recombinant interleukins or activated by specific antibodies. Infused back to the patient, modified lymphocytes start destroying the malignant cells.
Role of the targeted treatment
Targeted therapy has already been included into the gastric cancer international treatment protocols. Trastuzumab was established as the higher-priority option for patients with inoperable gastric tumors and positive HER2 status. Trastuzumab is a monoclonal antibody that specifically targets human epidermal growth factor receptor 2 (HER2). As the long-term observation has demonstrated its safety and effectiveness, scientists began to explore new molecules and treatment modes:
- Tyrosine kinase inhibitors targeting EGFR/HER-2 Lapatinib.
- Monoclonal antibodies against EGFR Cetuximab, Panitumumab, and Nimotuzumab.
- Monoclonal antibodies against VEGF Bevacizumab.
Targeted therapy is investigated in a number of ongoing clinical trials, like GATSBY, AVAGAST, ENRICH, INTEGRATE, and others.
What to do if immunotherapy is not available in your country yet
Due to the peculiarities of legislation in the medical sphere, novel treatment options often need to be approved by the local authorities. This process may take few months, so patient need to wait and miss the opportunity to start treatment at an earlier stage. Fortunately, worlds leading hospitals offer state-of-art stomach cancer treatment regardless of the patients origin country.
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