Background
Approximately 60% of newly diagnosed rectal cancers are locally advanced. The standard of care for these malignancies is treating with DNA-damaging agents, neoadjuvant chemoradiation therapy (nCRT) or radiation, followed by surgery. Unfortunately, 70-80% of patients experience less than a complete response, but are not spared the toxicity of CRT. At present, there is no clinically actionable biomarker to predict which patients are likely to respond to nCRT. A biomarker of nCRT response will allow precision treatment, leading to improved clinical outcomes.
Summary of the Invention
Researchers from Fox Chase Cancer Center developed a new technology to detect therapeutic response in rectal cancers, based on solid science as follows. Patients with poor DNA damage repair mechanisms have a more favorable response to DNA damaging treatments. Gamma-H2AX (γH2AX) is a phosphorylated H2AX histone that is used as a marker of DNA double stand breaks and cellular response to DNA damage. The study aimed to determine whether differences in the γH2AX levels of pre-treatment peripheral blood lymphocytes (PBLs) of rectal cancer patients were predictive of their response to nCRT. The data showed that rectal cancer patients who differ in their response to nCRT also differ in DNA-Damage Recognition and Repair (DRR) capacity, suggesting that DNA-DRR capacity can form the basis of a biomarker. As γ-H2AX and other DNA-DRR biomarkers were evaluated in pPBLs (germline DNA), the latter, either treatment-naïve or post-treatment, can be used for the analyses.
Advantages
- Biomarker of chemoradiation therapeutic benefit in rectal cancers that can be extended to all solid tumors
- Easy to perform screening, utilizing peripheral blood lymphocytes and their germline DNA
- Diagnostic method leading to precision cancer treatment aiming to improve clinical outcomes
IP Status
International patent application has been published (WO 2018/152154 A1)
For Partnering/Licensing information, please contact:
Inna Khartchenko, MS, MBA
Director, Technology Transfer and New Ventures
Inna.Khartchenko@fccc.edu