Page 12 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Chapter 1
General introduction
In this context, it is also important to mention the potential to escape immune system surveillance. Furthermore, the accumulation of mutation and genome instability results in an ever-expanding expansion of subclones of the tumor cells, which will be subject to selection (also in response to therapy). As mentioned many tumors promote inflammation, causing normal immune cells to infiltrate and also attack the tumor cells. But this beneficial effect is often counterbalanced by the resulting inflammation-dependent promotion of tumor growth, activation of pro-survival pathways and release of proangiogenic factors (Fig. 1B)(3). A block of differentiation can be distinguished as another hallmark of cancer, and this is caused by the ectopic expression or loss of key transcription factors. In this thesis, I try to take all of these factors into account in an effort to explain the cancer process.
In essence, genetic and epigenetic alterations are the underlying causes for these cancer hallmarks to appear. These epigenetic changes prominently include DNA methylation and covalent histone modifications, whereas the genetic changes involve processes such as deletion, amplification, insertion, translocation or point mutations, in addition to changes in the expression levels of the affected genes or changes in enzymatic activity. In conjunction, these changes provoke the appearance of the above-described cancer hallmarks. The genetic alterations can be inherited or acquired due to exposure to environmental factors, like tobacco smoking, or can be associated with specific dietary habits (high-fat), contact with toxic chemicals or viral and/or bacterial infection. If these genetic changes provide the cells with a selective advantage, this results in their outgrowth within the local tissue. Further accumulation of genetic changes because of genome instability, can then promote tumor cells to acquire increased invasive and metastatic potential[2]. It is, however, fair to say that in many cases we only poorly understand how all these effects conspire to provoke disease.
Understanding cancer thus represents one of the significant challenges for the scientific community in the present century. Some types of cancer have a more substantial impact on public health as they present with higher incidence and mortality, among them gastrointestinal cancer. In the general introduction of this thesis, I present an overview of the current knowledge on gastric cancer, addressing epidemiological, clinicopathological and biological aspects.
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