# Methionine Dependency of Cancer

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $168,019

## Abstract

Project Summary
Over 30 years ago it was discovered that cancer cells show a unique metabolic requirement for
methionine that separates them from normal cells. This phenomenon is called “methionine
dependence of cancer” or “methionine sensitivity of cancer” and describes the growth behavior of
cancer cells when methionine is replaced with its immediate metabolic precursor homocysteine. While
non-tumorigenic cells proliferate at normal rates in homocysteine medium, the overwhelming majority
of cancer cells induces cell cycle arrest followed by apoptosis when cultured in homocysteine
conditions. While conversion of homocysteine to methionine is not defective in cancer cells, these
growth conditions appear to reduce the flux through the one-carbon cycle, which seems to primarily
affect cancer cell growth. The dependence on high metabolic flux through methionine metabolism is
also observed in solid tumors and leukemias. While the phenomenon of methionine sensitivity of
cancer promises great therapeutic potential, it has been difficult to sufficiently reduce methionine
availability in patients to trigger tumor regression through dietary restrictions alone. It is thus essential
to understand the underlying mechanisms that govern methionine dependence of cancer. We
therefore respond to the NCI’s provocative question 11 (Through what mechanisms do diet and
nutritional interventions affect the response to cancer treatment?) and aim to understand molecular
mechanisms that trigger methionine sensitivity of cancer, and discover treatment modalities that are
enhanced by reduced methionine availability.

## Key facts

- **NIH application ID:** 10016225
- **Project number:** 5R21CA242270-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Peter Kaiser
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $168,019
- **Award type:** 5
- **Project period:** 2019-09-11 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016225

## Citation

> US National Institutes of Health, RePORTER application 10016225, Methionine Dependency of Cancer (5R21CA242270-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10016225. Licensed CC0.

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