Megh Gore

Introduction. Gastric cancer, the fifth most common cancer in the world and the third most common cause of cancer-related deaths, is often diagnosed in later stages leading to increased morbidity and mortality.¹ Factors such as H. pylori, smoking, alcohol, and genetics play a role in the increase incidence and poor prognosis of gastric cancer.¹ A factor of this poor prognosis is the increase in number of tumor associated macrophages (TAMs), due to increased prolonged levels of H. pylori, lactate, and Colony Stimulating Factor-1 (CSF-1).^1,2 An increase in levels of M2 TAMs lead to increased angiogenesis, tumor growth, and metastasis.^1,3 By identifying increased levels of and inhibiting the CSF-1/CSF-1R axis, it may be possible to improve gastric cancer outcomes. Methods. Immunohistochemical studies were done on 148 tissue samples collected during surgery on gastric cancer patients using avidin-biotin-peroxidase methods, primary antibodies, and goat polyclonal antibodies against CSF-1.⁴ Samples were also analyzed using PCR after reverse transcription analysis to measure CSF-1 and CSF-1R levels in the tissue samples.⁴ Patients were then sorted into high and low categories for both CSF-1 and CSF-1R and their 5-year survival was measured at 10-month intervals.⁴ In a phase Ia/b study, patients with solid tumors were treated with Emactuzumab, a monoclonal antibody to CSF-1R, either as a monotherapy or in combination with paclitaxel.⁵ Optimal biological dose as well as biopsies to detect tumor progression and M2 macrophage levels were taken before and during treatment.⁵ Results. Immunohistochemical analysis shows an increased level of both CSF-1 and CSF-1R in gastric cancer tissues.⁴ Patients who were classified to have high expression of CSF-1 or CSF-1R were found to have increased mortality over five years in comparison to those in the low expression groups.⁴ Patients treated with the monoclonal antibody showed no maximum tolerated dose and no antitumor activity as a monotherapy or in combination with paclitaxel.⁵ Treatment with Emactuzumab showed a decrease in M2 TAMs. Conclusions. The CSF-1/CSF-1R axis is elevated in gastric cancer tissues, signaling an important association. While a monoclonal antibody to CSF-1R did not decrease tumor size or inhibit cancer growth, the decrease in M2 macrophage numbers shows a promising avenue for an adjunct cancer therapy. Additionally, the relationship between elevated CSF-1 and gastric cancer may be able to serve as an important clinical tool, helping with early diagnosis.

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