In the palliative situation, combination chemotherapy with two drugs has been shown to be effective, both in patients with adeno-and Nutlin 3a squamous cell carcinoma. Effectiveness can be further increased with a triple combination in patients with adenocarcinoma, at the cost of increased side effects. Addition of monoclonal antibody trastuzumab in HER2 positive metastatic gastroesophageal junction cancer increases OS even further. Second-line therapy after failure of first-line therapy or tumor recurrence is still experimental, but docetaxel monotherapy, and targeting VEGF-R2 with ramucirumab have improved OS, according to two separate Phase III studies.
In the past, many different predictors for response of AC/SCC to chemotherapy/chemoradiation have been investigated, ranging from simple histology to various molecular markers, such as p53, proliferative cell nuclear antigen, EGFR, Ki-67, cyclin D1, expression of thymidylate synthase, and microvessel density, in both tissue and serum. None are reliable, and results cannot help clinical decision making. Metabolic imaging with positronemission tomography scanning is promising, with its ability to predict response early in the course of treatment.112 Therefore, definition of predictive and prognostic factors, optimization of chemo- and chemoradiation regimens and evaluation of the role of molecular-targeted therapy are the goal of current studies. One major limitation to cancer therapies results from the heterogeneity of the cancer cells even within a single tumor.
As tumors increase in size, many cancer cells grow distant from the blood supply, which may cause them to divide less frequently than others in the population. In addition, with increasing numbers of cancer cells, there is an increase in genetic mutations with each generation that will help cancer cells to escape the toxicity of treatment. It is, therefore, a big challenge to target these treatment-resistant cancer cells that are responsible for disease recurrence. The combination of therapeutic regimens that target different mechanisms of cancer cell development to provide the maximal cell killing without increasing toxic side effects to the patient is, therefore, mandatory. Footnotes Disclosure The authors report no conflicts of interest in this work.
adipose tissue plays a critical role in energy homeostasis by providing fatty acids (FA) as an oxidative fuel for other tissues.
It also secretes biologically active, hormone-like adipokines that target various peripheral tissues and the brain (3). The transport of FA into adipocytes is mediated by FA transport protein-1 (FATP1) and the scavenger receptor FAT/CD36 (11). Insulin increases FA uptake in adipocytes by stimulating the translocation of FATP1 from intracellular vesicles to the plasma Drug_discovery membrane (40).