Cancer stem cells in colorectal cancer: Signaling pathways involved in stemness and therapy resistance

Nasim Ebrahimi; Maral Afshinpour; Siavash Seifollahy Fakhr; Paniz Ghasempour Kalkhoran; Vida Shadman-Manesh; Samaneh Adelian; Sheida Beiranvand; Fatemeh Rezaei-Tazangi; Roya Khorram; Michael R Hamblin; Amir Reza Aref

doi:10.1016/j.critrevonc.2023.103920

Cancer stem cells in colorectal cancer: Signaling pathways involved in stemness and therapy resistance

Crit Rev Oncol Hematol. 2023 Feb:182:103920. doi: 10.1016/j.critrevonc.2023.103920. Epub 2023 Jan 23.

Affiliations

¹ Division of Genetics, Department of cell and molecular & microbiology, Faculty of Science and technology, University of Isfahan, Isfahan, Iran.
² Department of chemistry and Biochemistry, South Dakota State University (SDSU), Brookings, SD, USA.
³ Department of Biotechnology; Faculty of Applied Ecology, Agricultural Sciences and Biotechnology, Campus Hamar, Norway.
⁴ Department of Cellular and Molecular Biology_Microbiology, Faculty of Advanced Science and Technology, Tehran Medical science, Islamic Azad University, Tehran, Iran.
⁵ Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran.
⁶ Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
⁷ Department of Biotechnology, School of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
⁸ Department of Anatomy, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.
⁹ Bone and Joint Diseases Research Center, Department of Orthopedic Surgery, Shiraz University of Medical Sciences, Shiraz, Iran.
¹⁰ Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa. Electronic address: labhamblin@gmail.com.
¹¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Xsphera Biosciences, Translational Medicine Group, 6 Tide Street, Boston, MA 02210, USA. Electronic address: amir@xspherabio.com.

PMID: 36702423
DOI: 10.1016/j.critrevonc.2023.103920

Abstract

Colorectal cancer (CRC) is the third cause of cancer death worldwide. Although, in some cases, treatment can increase patient survival and reduce cancer recurrence, in many cases, tumors can develop resistance to therapy leading to recurrence. One of the main reasons for recurrence and therapy resistance is the presence of cancer stem cells (CSCs). CSCs possess a self-renewal ability, and their stemness properties lead to the avoidance of apoptosis, and allow a new clone of cancer cells to emerge. Numerous investigations inidicated the involvment of cellular signaling pathways in embryonic development, and growth, repair, and maintenance of tissue homeostasis, also participate in the generation and maintenance of stemness in colorectal CSCs. This review discusses the role of Wnt, NF-κB, PI3K/AKT/mTOR, Sonic hedgehog, and Notch signaling pathways in colorectal CSCs, and the possible modulating drugs that could be used in treatment for resistant CRC.

Keywords: Cancer initiating cells; Cancer stem cells; Cellular metabolism; Colorectal cancer; Drug resistance; Signaling pathways.

Publication types

Review

MeSH terms

Colorectal Neoplasms* / drug therapy
Colorectal Neoplasms* / metabolism
Hedgehog Proteins / metabolism
Humans
Neoplastic Stem Cells / pathology
Phosphatidylinositol 3-Kinases* / metabolism
Signal Transduction

Substances

Phosphatidylinositol 3-Kinases
Hedgehog Proteins