Targeting Cancer Cell Subsets

Understanding the Heterogeneity of Cancer Cell Populations

Despite current advances in cancer therapy, tumor recurrance and metastases remain clinical challenges.1 A potentional new approach to address these is the simultaneous targeting of mature, differentiated tumor cells and an undifferentiated subset of the tumor cell population known as cancer stem cells (CSCs).2,3 The heterogeneity of the tumor due to this spectrum of cell subsets points to the need for multitargeted approaches.1

A Closer Look at Two Cancer Cell Subsets That May Drive Tumor Progression

At a high level, cancer cells can be categorized into two subsets: differentiated cancer cells and undifferentiated CSCs. Differentiated cancer cells sustain and increase the volume of local tumors but lack the ability to self-renew. CSCs, however, possess the ability to self-renew and differentiate, which enables them to originate tumors and metastasize.3,5

Notably, cancer cells can also dedifferentiate in response to multiple stimuli, possibly including conventional cancer therapies.3,6

The Persistance of CSCs May Help Explain Tumor Recurrence

While conventional therapies kill the bulk of differentiated cancer cells, resulting in tumor shrinkage, CSCs may remian viable and later reestablish the tumor, leading to relapse.7 The persistence of CSCs despite therapy could help explain why some tumors recur even after an initial reduction in size.8

Therefore, targeting both CSCs and differentiated cancer cells may be a rational therapeutic strategy.2

Boston Biomedical is a leading developer of the next-generation of cancer therapeutics designed to inhibit multiple oncogenic pathways.

References

  1. Yoshida GJ. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res. 2015;34:111.doi:10.1186/s13046-015-0221-y.
  2. Visvader J, Lindeman G. Cancer stem cells: current status and evolving complexities. Cell Stem Cell. 2012;10(6):717-728.
  3. 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.
  4. Brooks MD, Burness ML, Wicha MS. Therapeutic implications of cellular heterogeneity and plasticity in breast cancer. Cell Stem Cell. 2015;17(3):260-271.
  5. 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.
  6. 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.
  7. Reya T, Morrison S, Clarke M, Weissman I. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105-111.
  8. 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.