Viability Assessment Following Anticancer Treatment Requires Single-Cell Visualization

Area of Science:

• Oncology
• Cell Biology
• Cancer Research

Background:

• Anticancer treatments can induce dormant cancer cells, characterized by sustained proliferation arrest.
• These dormant cells, though appearing non-viable in assays, remain metabolically active and can promote tumor regrowth.
• Cancer cells can also survive genotoxic stress through anastasis, a reversal of apoptosis.

Purpose of the Study:

• To review findings on dormant and anastatic cancer cells.
• To discuss the importance of single-cell analysis for assessing cancer cell viability and metabolic activity.
• To highlight limitations of population-averaged assays in cancer research.

Main Methods:

• Review of existing literature on cancer cell dormancy and anastasis.
• Analysis of single-cell data from adherent cultures of solid tumor-derived cell lines.
• Assessment of metabolic activity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assays.

Main Results:

• A subset of tumor cells enter dormancy post-treatment, remaining viable and secreting growth factors.
• Single-cell analysis showed that nearly all long-term adherent cells exhibit metabolic activity (MTT metabolism) after anticancer treatment.
• Cellular size and morphology were poor indicators of viability in post-treatment cultures.

Conclusions:

• Single-cell observation methods are crucial for accurately assessing cancer cell viability and metabolic activity.
• Conventional preclinical assays may underestimate the persistence and viability of cancer cells post-treatment.
• Understanding dormant and anastatic cancer cell biology is vital for developing effective cancer therapies.