Colorectal cancer (CRC) ranks as the third most common cancer globally and second in terms of mortality . Although CRC incidence rates are higher in high-income compared with low-to-middle-income countries (LMICs), mortality is higher in LMICs.~Extensive research within the last decade has shown that silymarin can suppress the proliferation of a variety of tumor cells; this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors, down-regulation of anti- apoptotic gene products, inhibition of cell-survival kinases and inhibition of inflammatory transcription factors (e.g., Nuclear Factor- kappa B) through suppression of Nuclear Factor- kappa B-regulated gene products, including Cyclooxygenase-2, Lipoxygenase, Tumor necrosis factor and Interleukin-1. Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (Epidermal Growth Factor Receptor, Cyclooxygenase-2), invasion (Matrix metallopeptidase 9), angiogenesis (Vascular Endothelial growth Factor) and metastasis (adhesion molecules). Silymarin was reported to alter the expression of apoptosis-related proteins including BCL2 associated X protein to induce apoptosis in human gastric cancer cells in a concentration-dependent manner. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down-regulation of the Multidrug resistance protein and other mechanisms. In addition to its chemo-preventive effects, silymarin exhibits antitumor activity against human tumors in rodents. so we aim to assess the antitumor activity of silymarin in metastatic colorectal cancer patients receiving chemotherapy.
this work is aim to assess the antitumor effect of silymarin in patients with metastatic colorectal cancer receiving chemotherapy with or without target therapy (Bevacizumab).