Nanotechnology for colorectal cancer detection and treatment

Table 1 Stages of colorectal cancer development and progression

Stage	Progression	Metastasis
0	Unusual abnormal cells arise from mucosa of the colonic wall, eventually becoming cancerous and known as carcinoma in situ or intramucosal carcinoma	No
I	Cancerous cells spread from the mucosa to submucosa and may also extended until the muscularis propria	No
II
IIA	Cancerous cells spread out from the submucosa to serosa (outermost layer) of the colon wall	No
IIB	Cancerous cells spread through serosa but are not extended to nearby organs	No
IIC	Cancerous cells spread to nearby organs	No
III
IIIA	In the first case, cancerous cells grow through the mucosa into submucosa and also may extended until the muscularis propria. The cancer spread to 1 to 3 nearby lymph nodes or into the areas of fat near lymph nodes but not to distant sites	No
	In the second case, the cancer has spread through the mucosa into submucosa and has spread to 4 to 6 nearby lymph nodes
IIIB	In the first case, cancerous cells have spread through the muscularis propria of colon and/or rectum up to serosa or through the serosa to tissues and visceral peritoneum. They have also spread to 1 to 3 nearby lymph nodes or cancer cells are present in nearby tissues of lymph nodes but have not spread to distant sites	No
	Second case, the cancer has spread into the muscularis propria or into the outermost layers of colon or rectum and has spread to 4 to 6 nearby lymph nodes but not to distant sites
	Third case, the cancer has spread through the mucosa into submucosa and it might also have grown into the muscularis propria of colon and/or rectum and has spread to 7 or more nearby lymph nodes but not to distant sites
IIIC	First case, the cancer has grown through the serosa colon and/or rectum to visceral peritoneum but has not reached nearby organs. It has spread to 4 to 6 nearby lymph nodes but not to distant sites	No
	Second case, the cancer has grown into the outermost layers of the colon and/or rectum or through visceral peritoneum but has not reached nearby organs. It has spread to 7 or more nearby lymph nodes but not to distant sites
	Third case, the cancer has grown through the wall of the colon and/or rectum and is attached to or has grown into other nearby tissues or organs. It has spread to at least one nearby lymph node or into areas of fat near the lymph nodes but not to distant sites
IV
IVA	The cancer has spread to one area or organ that is not near the colon and/or rectum, may be liver, lung, ovary, or a distant lymph node	Yes
IVB	The cancer has spread to more than one area or organ that is not near the colon and/or rectum, such as the liver, lung, ovary, or a distant lymph node	Yes
IVC	The cancer has spread to the tissue that lines the wall of the abdomen and may have spread to other areas or organs	Yes

Table 2 Screening methods for colorectal cancer

Ref.	Screening methods
[18-20]	Stool tests	Kit-based technique; guaiac-based fecal occult blood test uses guaiac to detect heme; FIT uses antibody to detect hemoglobin in stool; FIT-DNA test detects hemoglobin and DNA biomarkers in the stool
		Non-invasive, low cost, colon cleansing is not required, non-bleeding tumors cannot be detected
[21,22]	Flexible sigmoidoscopy	Flexible tube with light, lens for viewing and tool for removing tissue; rectum and lower third of the colon screened to detect polyps, cancer or other abnormalities
		Sedation is required; accurate detection if polyps and cancers are present; unable to detect polyps or any abnormalities present in cecum, ascending colon hepatic flexure, or on transverse colon; colon cleansing is required
[23,24]	Colonoscopy	Flexible tube light with a lens for seeing and a tool for excising the abnormal tissue; entire colon and rectum are screened for cancer by inserting the colonoscope through anus
		Sedation is required; visualization of entire inner lining of the colon and rectum; minute polyps can be detected; sedation may lead to bleeding or tear of the intestinal wall; sedation may lead to bleeding or tear of the intestinal wall
[25-27]	Computed tomography colonography	X-ray based computed tomography scanner captures two- and three-dimensional images of the entire colon; computer assembles these pictures into detailed images
		Sedation is not required in this method; non-invasive; colon cleansing is not essential; may miss small polyps
[28]	Double-contrast barium enema	X-ray images are then captured by introducing barium sulphate enema
		Examination of the whole colon and the rectum; sedation is not required; for the patient who cannot undergo standard colonscopy, this method is useful; colon cleansing is very necessary for this method; otherwise, it will give false positive results

FIT: Fecal immunochemical test.

Table 3 Currently available colorectal cancer treatment methods

Treatment methods	Types/medication details	Side-effects	Stages	Ref.
Surgery	Laparoscopic surgery	Pain; tenderness; irritation and itching; constipation or diarrhea	I, II, III, IV	[32,44]
	Colostomy for rectal cancer
	Radiofrequency ablation or cryoablation
Radiation therapy	External-beam radiation therapy	Fatigue; mild skin reactions; bleeding in stools; constipation or diarrhea; infertility	II, III, IV	[33,34]
	Stereotactic radiation therapy
	Intraoperative radiation therapy
	Brachytherapy
Chemotherapy	Capecitabine (Xeloda)	Vomiting; nausea; diarrhea; mouth sores; neuropathy; fatigue; hair loss	II, III, IV	[36,39]
	Fluorouracil
	Irinotecan (Camptosar)
	Oxaliplatin (Eloxatin)
	Trifluridine/tipiracil (Lonsurf)
Targeted therapy	Anti-angiogenesis therapy	Rashes	IV	[38,45]
	Epidermal growth factor receptor inhibitors
	Combined targeted therapies
	Tumor-agnostic treatment
Immunotherapy	Pembrolizumab (Keytruda)	Fatigue; rashes, pain and itching; diarrhea; nausea; fever; vomiting; shortness of breath	III, IV	[46,47]
	Nivolumab (Opdivo)
	Dostarlimab (Jemperli)
	Nivolumab and ipilimumab (Yervoy) combination