Hallmarks in colorectal cancer: angiogenesis and cancer stem-like cells.
Carcinogenesis is a multistep process that requires the accumulation of various genetic and epigenetic aberrations to drive the progressive malignant transformation of normal human cells. Two major hallmarks of carcinogenesis that have been described are angiogenesis and the stem cell characteristic of limitless replicative potential. These properties have been targeted over the past decade in the development of therapeutic treatments for colorectal cancer (CRC), one of the most commonly diagnosed and lethal cancers worldwide. The treatment of solid tumor cancers such as CRC has been challenging due to the heterogeneity of the tumor itself and the chemoresistance of the malignant cells. Furthermore, the same microenvironment that maintains the pool of intestinal stem cells that contribute to the continuous renewal of the intestinal epithelia also provides the necessary conditions for proliferative growth of cancer stem-like cells. These cancer stem-like cells are responsible for the resistance to therapy and cancer recurrence, though they represent less than 2.5% of the tumor mass. The stromal environment surrounding the tumor cells, referred to as the tumor niche, also supports angiogenesis, which supplies the oxygen and nutrients needed for tumor development. Anti-angiogenic therapy, such as with bevacizumab, a monoclonal antibody against vascular-endothelial growth factor, significantly prolongs the survival of metastatic CRC patients. However, such treatments are not completely curative, and a large proportion of patient tumors retain chemoresistance or show recurrence. This article reviews the current knowledge regarding the molecular phenotype of CRC cancer cells, as well as discusses the mechanisms contributing to their maintenance. Future personalized therapeutic approaches that are based on the interaction of the carcinogenic hallmarks, namely angiogenic and proliferative attributes, could improve survival and decrease adverse effects induced by unnecessary chemotherapy.
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Carole Melin, Department of Digestive Surgery, Limoges University Hospital, 87042 Limoges, France.
Muriel
M
Mathonnet
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Carole Melin, Department of Digestive Surgery, Limoges University Hospital, 87042 Limoges, France.
Aurelie
A
Perraud
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Carole Melin, Department of Digestive Surgery, Limoges University Hospital, 87042 Limoges, France.
Niki
N
Christou
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Carole Melin, Department of Digestive Surgery, Limoges University Hospital, 87042 Limoges, France.
Hussein
H
Akil
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Carole Melin, Department of Digestive Surgery, Limoges University Hospital, 87042 Limoges, France.
Carole
C
Melin
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Carole Melin, Department of Digestive Surgery, Limoges University Hospital, 87042 Limoges, France.
Serge
S
Battu
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Carole Melin, Department of Digestive Surgery, Limoges University Hospital, 87042 Limoges, France.
Marie-Odile
MO
Jauberteau
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Carole Melin, Department of Digestive Surgery, Limoges University Hospital, 87042 Limoges, France.
Yves
Y
Denizot
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000860:Hypoxia; D007422:Intestines / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000166:cytology*; D009389:Neovascularization, Pathologic; D016896:Treatment Outcome; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
Cancer stem-like cell; Colon cancer; Microenvironment; Stem cell; Tumor-initiating cell