**2. Conventional options for colorectal cancer treatment**

The treatment of colon cancer is mainly well-known in three types: surgery, chemotherapy, and radiation therapy, and appropriate options are selected according to the stage of colorectal cancer between these therapies [3]. The progression of colorectal cancer is divided into stages from 0 to 4. Most cases of stage 0 colorectal cancer are forming as polyps that do not grow beyond the inner lining of the colon or rectum, the local lesions are excised through a colonoscopy or transanal resection [3, 4]. Stage 1 colorectal cancer has grown deeper into the layer of the colon or rectal wall, but it means that the cancer cells do not spread outside of the colon or rectal wall or into the nearby lymph nodes [3, 4]. Complete removal of polyps is done during the colonoscopy, and if cancer cells are not found at the edge of lesions after removal, no other treatment may be needed [3, 5]. Stage 2 means that the cancer cells have grown into nearby tissues outside the walls of the colon or rectum but have not spread to the lymph nodes [3, 4]. Treatment may require partial colectomy, which removes the portion of the colon or rectum that contains cancer along with the surrounding lymph nodes. If the risk of cancer recurrence is high, adjuvant chemotherapy may be

recommended according to the status of microsatellite instability or mismatch repair gene expression [3, 5]. The main options for chemotherapy include a combination of 5-FU and leucovorin with oxaliplatin (FOLFOX) or capecitabine (XELOX), but other combinations are also available including radiation followed by surgery [6–8]. Stages 3 and 4 are belonging to advanced, refractory colorectal cancer, which means that spreads to nearby lymph nodes or distant organs (mainly the liver or lungs) [3, 4]. At these stages of colon cancer, surgery to remove the cancerous portion of the colon along with nearby lymph nodes followed by adjuvant chemotherapy is the standard treatment for this stage. For rectal cancer, FOLFOX, XELOX, or capecitabine alone is given along with radiation therapy followed by surgery to remove rectal cancer and nearby lymph nodes, usually by low anterior resection, proctectomy with coloanal anastomosis, or abdominoperineal resection [5–7]. If primary or spread colorectal cancer cannot be completely removed with surgery, treatment options are likely to be selected with chemo or targeted therapies, such as 5-FU, oxaliplatin, irinotecan, capecitabine, bevacizumab, cetuximab, and/or regorafenib used alone or in combination [3, 6, 7]. A relatively wide range of treatment options depending on the stage of colorectal cancer may give hope to the patients for a cure, and providing a variety of options to physicians can also have important implications in terms of effective cancer management in clinical. However, it should not be overlooked that even in the presence of these known options, colorectal cancer has not yet been conquered. This is because even if these standard options are applied, there are still limitations in treatment. Briefly, recurrence after surgery, resistance to chemotherapies by mutations, and side effects of radiation therapy have been considered the main difficulties, therefore attempts to find bettered therapeutics to overcome these limitations are undergoing.
