The Role of Cancer Stem Cells (CSCs) and Cancer Stemness in Recurrence and Metastasis1
Despite current advances in cancer therapy, tumor recurrence and metastases remain clinical challenges.1 A potential new approach to address these is the targeting of a subset of the tumor cell population known as CSCs.2
CSCs are highly tumorigenic, have high metastatic potential, and are resistant to conventional cancer therapies.3
CSCs also possess stemness, which is the ability to self-renew and differentiate.4 Stemness may enable CSCs to metastasize and regrow tumors.3
The CSC Model May Help Explain Tumor Recurrence
In the clonal evolution model, all cells within a malignant tumor have similar tumorigenic activity.5 By contrast, in the CSC model only a subset of tumor cells, CSCs, have tumor-initiating capability.2 This may help to explain why early tumor shrinkage is often poorly predictive of overall survival.6,7 While conventional chemotherapies kill the bulk of non-stem cancer cells, resulting in tumor shrinkage, CSCs may remain viable and later reestablish the tumor, potentially leading to relapse.4
Stemness of CSCs May Drive Tumor Growth
Cancer stemness can be acquired by non-stem cancer cells as they dedifferentiate in response to multiple stimuli, possibly including conventional cancer therapies.8,9 In fact, an unintended result of treatment with chemotherapy or radiotherapy may be enrichment of the CSC fraction of a tumor.8,10
Emerging research suggests that targeting both the non-stem cancer cell and CSC subpopulations may be necessary to eliminate the entire cancer cell population. As the understanding of CSCs progresses, the identification of CSC-specific therapeutic agents may lead to advances in cancer treatments.10
Boston Biomedical is developing the next generation of cancer therapeutics with drugs designed to inhibit cancer stemness pathways.
- Li Y, Rogoff H, Keates S, et al. Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc Natl Acad Sci U S A. 2015;112(6):1839-1844.
- Fanali C, Lucchetti D, Farina M, et al. Cancer stem cells in colorectal cancer from pathogenesis to therapy: controversies and perspectives. World J Gastroenterol. 2014;20(4):923-942.
- Botchkina G, Ojima I. Prostate and colon cancer stem cells as a target for anti-cancer drug development. In: Shostak S, ed. Cancer Stem Cells: Theories and Practice. Rijeka, Croatia: InTech; 2011.
- Reya T, Morrison S, Clarke M, Weissman I. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105-111.
- Marjanovic N, Weinberg RC, CL. Cell plasticity and heterogeneity in cancer. Clin Chem. 2013;59(1):168-179.
- Coart E, Saad E, Shi Q, et al. Trial-level association between response-based endpoints and progression-free/overall survival in 1st-line therapy for metastatic colorectal cancer in the ARCAD database. J Clin Oncol. 2015;33(suppl 3; abstr 666).
- Zabor E, Heller G, Schwartz L, Chapman P. Correlating surrogate endpoints with overall survival at the individual patient level in BRAFV600E-mutated metastatic melanoma patients treated with vemurafenib. Clin Cancer Res. 2016;22(6):1341-1347.
- Lagadec C, Vlashi E, Della Donna L, Dekmezian C, Pajonk F. Radiation-induced reprogramming of breast cancer cells. Stem Cells. 2012;30(5):833-844.
- Fabregat I, Malfettone A, Soukupova J. New insights into the crossroads between EMT and stemness in the context of cancer. J Clin Med. 2016;5(3):E37.
- Li X, Lewis M, Huang J, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100(9):672-679.