Cancer Stem Cells (CSCs)
CSCs’ Role in Cancer 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
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 therapies kill the bulk of non-stem cancer cells, resulting in tumor shrinkage, CSCs may remain viable and later reestablish the tumor, leading to relapse.4
- 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.