5-FU in combination with PARP inhibitor ABT-888 deregulates MGMT-dependent mismatch repair (MMR) pathway in MMR-proficient colorectal cancer stem cells by modulating MGMT/PARP1/MSH6 complex
- Published on 07/28/2026
- Reading time: 1 min.
Subarno Paul a , Chinmay Das a , Subhasmita Bhal a , Saptarshi Sinha a , Somya Ranjan Dash a , Sushree Subhadra Acharya a , Aakash Goswami a , Kunal Goutam b , Chanakya Nath Kundu a & Tithi Parija a,*
a Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to Be University, Bhubaneswar, India
b Department of Surgical Oncology, Acharya Harihar Post Graduate Institute of Cancer, Cuttack, India
CONTACT Tithi Parija mailto:tithi.parija@kiitbiotech.ac.in Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to Be University, Campus-11, Patia, Bhubaneswar, Odisha 751024, India
Abstract
Background Previous study showed the PARP inhibitor ABT-888 potentiates the cytotoxicity of 5-fluorouracil (5-FU) by inhibiting PARP1-mediated mismatch repair (MMR) pathway via MSH6 deregulation in MMR-proficient colorectal cancer stem cells (CRC-CSCs). Emerging evidence indicates 5-FU regulates O6 -methylguanine-DNA-methyltrans ferase (MGMT) activity, but the mechanistic basis of MGMT involvement in PARP1-mediated MMR pathway following 5-FU treatment remains...
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