# Detecting Reversal of Apoptosis in Cancer Cells in Mice

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2024 · $221,911

## Abstract

Detecting Reversal of Apoptosis in Cancer Cells in Mice
Project Summary
Targeting apoptotic pathways is one of the most important therapeutic strategies for cancer treatments,
and primary cancers often exhibit dramatic initial responses to such treatments. However, most
metastatic cancers inevitably recur, leading to treatment failure. The classical view of apoptosis has
long assumed that, once initiated, this cell suicide process is irreversible. Challenging this assumption
is our recent highly original discovery that apoptosis can be reversible, even at late stages, in multiple
human cancer cell lines in vitro. We named this cell recovery mechanism “anastasis”, which means
“rising to life” in Greek. Removal of a death stimulus is sufficient to allow anastasis to occur, thus
indicating that anastasis is an intrinsic recovery phenomenon. We hypothesize that anastasis is an
unexpected escape tactic used by cancer cells to survive cell-death-inducing cancer therapy, thereby
causing cancer recurrence. If this hypothesis is true, anastasis would be a novel therapeutic target for
suppressing cancer recurrence and progression. However, anastasis in cancer cells in vivo has yet to
be demonstrated, and the consequences of anastasis remain undiscovered. To detect anastasis in live
animals, we have successfully developed a new biosensor to label anastatic cells in fruit flies, by
fluorescently tagging cells that have reversed apoptosis. This permanent tag is a unique tool for
detecting and following the consequences of anastasis in vivo. Here, we will apply the similar strategy
to detect and track anastasis in cancer cells in mice. By incorporating biosensor-expressing human
cancer cells with three clinically relevant xenograft mouse models of cancer relapse, we will determine
whether anastasis occurs in cancer cells in vivo, and if identified, whether it contributes to recurrence
after anti-cancer therapy. Our results will lay a strong foundation for developing anastasis-targeting
anti-cancer therapy, by generating essential animal models for studying the consequences of anastasis,
and by revealing the therapeutic potential of harnessing anastasis to suppress cancer recurrence.

## Key facts

- **NIH application ID:** 10785193
- **Project number:** 1R21CA286284-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ho Lam Tang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $221,911
- **Award type:** 1
- **Project period:** 2024-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785193

## Citation

> US National Institutes of Health, RePORTER application 10785193, Detecting Reversal of Apoptosis in Cancer Cells in Mice (1R21CA286284-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10785193. Licensed CC0.

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