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Background <p>Metabolic rewiring enables cancer cells to adapt to nutrient stress, making amino acid deprivation an attractive therapeutic strategy. However, cancer type–specific responsiveness to individual amino acid deprivation remains incompletely characterized.</p> Methods <p>We profiled the viability of 60 cancer cell lines from six tissue origins under deprivation of each of the 20 proteinogenic amino acids. Based on the screening, we evaluated the therapeutic interaction between cyst(e)ine deprivation or pharmacological inhibition of cyst(e)ine metabolism and carboplatin in ovarian cancer models. Transcriptomic analyses together with functional validation experiments were performed to explore potential molecular mechanisms.</p> Results <p>The unbiased screen revealed a relative sensitivity of ovarian cancer cells to cyst(e)ine deprivation. Cyst(e)ine starvation enhanced responsiveness to carboplatin in both carboplatin-sensitive and -resistant ovarian cancer cell lines. Pharmacological inhibition of cyst(e)ine metabolism showed a similar effect, supporting pharmacological targeting of cyst(e)ine metabolism as a potential alternative to dietary deprivation. Activating transcription factor 3 (ATF3) was identified as a candidate stress-responsive factor, and its suppression partially attenuated apoptotic marker induction, suggesting that ATF3 contributes, at least in part, to the stress-associated apoptotic response.</p> Conclusion <p>These findings suggest that cyst(e)ine metabolism may represent a therapeutically relevant metabolic target for enhancing carboplatin response in ovarian cancer. This screening framework provides a systematic approach to identify amino acid-associated metabolic dependencies with potential relevance in cancer therapy.</p>

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Metabolic targeting of cyst(e)ine enhances carboplatin responsiveness in ovarian cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Ina Yoon,
  • Sinae Oh,
  • Seo Young Park,
  • Jisu Park,
  • Hyelim Jang,
  • Eunji Park,
  • Kyung Ah You,
  • Kibum Kim,
  • Soonjae Hwang,
  • Hyeong Yun Kim,
  • Seongmin Cho,
  • Jung Min Han,
  • Sunghoon Kim

摘要

Background

Metabolic rewiring enables cancer cells to adapt to nutrient stress, making amino acid deprivation an attractive therapeutic strategy. However, cancer type–specific responsiveness to individual amino acid deprivation remains incompletely characterized.

Methods

We profiled the viability of 60 cancer cell lines from six tissue origins under deprivation of each of the 20 proteinogenic amino acids. Based on the screening, we evaluated the therapeutic interaction between cyst(e)ine deprivation or pharmacological inhibition of cyst(e)ine metabolism and carboplatin in ovarian cancer models. Transcriptomic analyses together with functional validation experiments were performed to explore potential molecular mechanisms.

Results

The unbiased screen revealed a relative sensitivity of ovarian cancer cells to cyst(e)ine deprivation. Cyst(e)ine starvation enhanced responsiveness to carboplatin in both carboplatin-sensitive and -resistant ovarian cancer cell lines. Pharmacological inhibition of cyst(e)ine metabolism showed a similar effect, supporting pharmacological targeting of cyst(e)ine metabolism as a potential alternative to dietary deprivation. Activating transcription factor 3 (ATF3) was identified as a candidate stress-responsive factor, and its suppression partially attenuated apoptotic marker induction, suggesting that ATF3 contributes, at least in part, to the stress-associated apoptotic response.

Conclusion

These findings suggest that cyst(e)ine metabolism may represent a therapeutically relevant metabolic target for enhancing carboplatin response in ovarian cancer. This screening framework provides a systematic approach to identify amino acid-associated metabolic dependencies with potential relevance in cancer therapy.