がんの科学と治療

Introduction: EGFR TKI has been widely studied in both research and clinic. However, only few limited studies focus on EGFR primary resistance rather than acquired mutation. Usually, EGFR T790M mutation is resistant to first generation TKI (erlotinib, gefitinib) and sensitive to third generation TKI Osimertinib. Here, we report an EGFR primary T790M and L858R double mutation patient confers clinical benefit to Erlotinib and resistance to Osimertinib.
Case presentation: Here we present a 70-year-old woman with lung adenocarcinoma harboredprimary T790M and L858R EGFR double mutation and underwent multiple lines of treatments. She benefited from the first-generation of EGFR TKI Erlotinib, and later quickly developed resistance to the third-generation TKI Osimertinib after disease progression, then followed a few rounds of chemotherapies. Multiple resistant EGFR mutations were detected, indicating frequent complex tumor heterogeneity in later stage patients caused by subclone evolution. Colonies with distinct Osimertinib resistance mutations included well known EGFR mutations L792V, L718V/R, G796S/A, and novel EGFR G729V and D1014V mutations, which are predicted to be acquired osimertinib resistance mutations by 3D-structural remodeling.
Conclusion: Our study revealed that EGFR primary T790M accompany with L858R mutation could benefit from erlotinib, and has stable disease for 7 months. The patient also benefited from chemotherapy for three months after resistance to osimertinib. ctDNA–based assay is a valuable tool for late stage cancer diagnosis, monitoring and intervention.

Cancer is a heterogeneous disease, the result of the specific combination of genetic and epigenetic changes in somatic cells, occurring as a cumulative process throughout the life of the human organism. The immune system is specialized to act in defense of our body, with potential of specific destruction without toxicity to the normal tissue. In the tumor context, this system acts both by actions of recognition and inhibition of development, as well as in tumor control through the interaction with cells that promote oncogenesis. As criteria to perform a systematic review of the literature understanding the relevance of the systemic-immune interaction and cancer, we select articles in the English language, with a descriptive an/or experimental design. Recognition of a tumor can be accomplished by identifying oncofetal antigens, proteins with altered structural conformation, abnormal expression of surface carbohydrates, as well as increased expression of proteins found in normal cells. In view of this recognition, antitumor responses may be cellular and/or humoral in nature, where cells of the immune system act by means of cytotoxic activity, or by releasing effector molecules. Like all immunological efforts, tumor cells are able to bypass the immune system through mutations in key molecules, loss of antigenicity and immunogenicity, changes in carbohydrate patterns, immunosuppressive activity of the tumor microenvironment, among others. Understanding the relationships between immune cells and cancer cells is essential for understanding the dynamics of cancer.

Transforming growth factor-beta (TGF-β) is a multifunctional cytokines of biologically active peptides. Recently years, the TGF-β was confirmed highly expressed in various types of human digestive system tumors. With the improvement of medical technology, the cure rate of early-stage tumor is obviously improved, but that of middleand advanced-stage tumors is still very low with poor prognosis. Therefore, it is important to explore a new targets, and increase the cure rate of malignant tumors and improve the life quality of patients. People have found that the tumor microenvironment (TME) can influence the tumors growth and evolution. The TME constituents such as pH, leukocytes, cytokines, extracellular matrix and humor, and contribute to the tumor cell proliferation, invasion and metastasis. There is plenty of evidence that TGF-β and their signaling play an important role in cell differentiation, inflammatory response, immunologic function and carcinogenesis in gastrointestinal cancers. The aims of this review is to provide a comprehensive view of TGF-β and its receptors and their function in the physiological and pathology mechanisms of the gastrointestinal cancers.