Biological Management of Gastrointestinal Cancers

Abstract

The management of gastrointestinal tumors has undergone a rapid change since the demonstrated effectiveness of biological treatment targeting its molecular markers. There have been a significant number of advances in the field of cancer biology that lead to improvement in the diagnosis and treatment of cancer including advances in defining the genetic and phenotypic changes in cancer cells, cellular targets for cancer diagnosis and therapy, the basic mechanisms of malignant transformation of cells including defect in apoptosis and cell cycle regulation, angiogenesis, and mechanism of tumor invasiveness and metastasis. This leads to increase in the importance of the role of prognostic markers in identifying patients at very low risk of disease events who can safely avoid treatment, or high-risk patients who may benefit from more aggressive treatment such as overexpression of vascular endothelial cell growth factor (VEGF), epidermal growth factor receptor (EGFR) andmatrix metalloproteinases (MMPs) indicating poor survival and increased tumour aggressiveness and metastatic potential. This leads to emergence of new groups of therapy such as anti-VEGF (Bevacuzimab), anti-EGFR (Cetuximab) and MMP inhibitors. There is also increase in the importance of the role of predictive tumour markers in managing a patient’s response to treatment leading to choosing the right drug for right patient such asHer-2 gene overexpression in gastric cancers and mutational status of Kras gene in cancer colon and CD117 (KIT) overexpression in gastrointestinal stromal tumors. In cancer colon, cetuximab can be used as monotherapy for the treatment of mCRC, and can also be used in second- and third-line combination therapy in patients with K-ras and B-raf wild type tumours with improvement in OS, PFS and overall response (OR). In gastric cancers, overexpression of the HER2 protein seems to possess the best predictive value for treatment with trastuzumab. In gastrointestinal stromal tumors, the presence of tumor KIT exon 11 mutation correlated with an improved objective response rate to imatinib, time to progression and overall survival when compared to patients with KIT exon 9 mutation. So, c-KIT has a prognostic and predictive value.

There are still many ongoing clinical trials that aim to know more information about biological therapy in gastrointestinal tumors and determining if therapy can improve survival and quality of life. Participation of large number of patients in multicenter trials should be encouraged to achieve a progress in gastrointestinal tumors treatment based on more studying of cancer biology and role and value of predictive and prognostic biological markers.