RESUMO
Neuroendocrine tumors (NETs) arise from cells distributed throughout the endocrine system. Although, NETs are heterogeneous in their behavior, they tend to be more aggressive when arising in the pancreas. Pancreatic NET (panNET) represents three percent of all primary pancreatic neoplasms. Symptomatic and progressive panNETs are generally treated with cytotoxic chemotherapy, whereas molecular targeted therapy is used for nonfunctional tumors without aggressive features. Pharmacogenetics has increasingly been used recently to better identify potential targets for therapy and help select patient-specific therapy. In this review, we discuss two abstracts (Abstracts #4113 and #e15169) presented at the ASCO Annual Meeting in Chicago this year, outlining the potential role of tumor gene and gene product profiling in disease management. We describe what is known about the pathogenesis of these tumors, role of decreased gene product expression (MGMT, RRM1, MET) and its application in cytotoxic therapy selection, as well as genetic mutations that can be used for molecular targeted therapy. With an overall shift towards personalized medicine, it has become ever more important to identify the molecular signature of a tumor as it appears to dictate the clinical behavior and response to therapy.
Assuntos
Antineoplásicos/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Farmacogenética/métodos , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Predisposição Genética para Doença/genética , Humanos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Farmacogenética/tendências , Proteínas Proto-Oncogênicas c-met/genética , Ribonucleosídeo Difosfato Redutase , Proteínas Supressoras de Tumor/genéticaRESUMO
We present the case of a 43-year-old-man with wild-type KRAS and BRAF colorectal adenocarcinoma that was metastatic to the liver and lung. The patient initially received neoadjuvant chemotherapy with FOLFOX and bevacizumab, followed by surgical resection of the primary tumor and hepatic metastases. His disease recurred shortly after surgery and he was treated with FOLFIRI plus the anti-EGFR antibody cetuximab. After this regimen failed to arrest his disease progression, treatment with FOLFIRI in combination with another anti-EGFR antibody, panitumumab was started. While on this therapy, the patient's lung nodules remained largely stable but metastatic lesions within the liver continued to progress. Our case highlights the differences between panitumumab and cetuximab, and contemplates the possible explanations for this patient's apparently heterogeneous disease progression within the liver despite stabilization of multiple pulmonary nodules.