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Colorectal Cancer Treatments and Studies / Genetic Factors in Colorectal Cancer · Review
Frontiers in Oncology · September 8, 2026
Raises a question worth testing. It does not answer one.
This retrospective case series describes two heavily pretreated patients with microsatellite-stable metastatic colorectal cancer and prior immune checkpoint inhibitor failure who received chidamide (a histone deacetylase inhibitor) combined with a PD-1 inhibitor, achieving one partial response and one stable disease. The authors explicitly acknowledge these observations are hypothesis-generating only and insufficient to demonstrate reversal of immunotherapy resistance or survival benefit; prospective studies are needed.
Retrospective case series. Two patients with microsatellite-stable metastatic colorectal cancer who had progressed on prior immune checkpoint inhibitor–containing regimens.. Intervention: Chidamide (selective histone deacetylase inhibitor) combined with PD-1 inhibitor (sintilimab in both cases; case 2 also received bevacizumab). n = 2.
Case 1: chidamide plus sintilimab achieved partial response with PFS of 6 months after prior progression on surufatinib plus camrelizumab (PFS 5 months, SD) Case 2: chidamide plus sintilimab plus bevacizumab achieved stable disease with PFS of 5.5 months after prior progression on surufatinib plus sintilimab (PFS 8.5 months, PR) No grade 3–4 adverse events occurred in either patient
No grade 3–4 adverse events occurred in either patient
These observations do not yet warrant clinical practice change. Clinicians should view this as a signal for future research; prospective biomarker-driven studies are needed to test whether epigenetic-immunotherapy combinations can overcome resistance in microsatellite-stable colorectal cancer.
A two-patient retrospective case series with mixed responses (one PR, one SD) in a heavily pretreated population; descriptive observations that generate hypotheses rather than test them and are explicitly insufficient to demonstrate efficacy or resistance reversal.
As stated by the source record.
Quoted from the source exactly as published.
These observations do not yet warrant clinical practice change. Clinicians should view this as a signal for future research; prospective biomarker-driven studies are needed to test whether epigenetic-immunotherapy combinations can overcome resistance in microsatellite-stable colorectal cancer.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background More than 90% of metastatic colorectal cancers (mCRC) are microsatellite-stable (MSS), an immunologically “cold” subtype characterized by low neoantigen burden, impaired antigen presentation, and poor responsiveness to immune checkpoint inhibitors (ICIs). Epigenetic aberrations—including aberrant DNA methylation and histone deacetylation—drive immune evasion in MSS CRC. Histone deacetylase inhibitors (HDACi) can restore major histocompatibility complex class I (MHC-I) expression, reshape the immunosuppressive tumor microenvironment (TME), and synergize with ICIs to enhance antitumor immunity. This retrospective study evaluated chidamide (a selective HDACi) plus a PD-1 inhibitor in two MSS CRC patients with prior ICI progression, with a mechanistic discussion informed by published evidence. Case presentation Case 1: A 60-year-old woman with BRAF V600E-mutant, right-sided, MSS mCRC received third-line surufatinib plus camrelizumab, with a best response of stable disease (SD) and a progression-free survival (PFS) of 5 months. After subsequent disease progression, fifth-line chidamide plus sintilimab achieved a partial response (PR), with a PFS of 6 months. Case 2: A 43-year-old man with recurrent RAS/BRAF wild-type MSS mCRC received fifth-line surufatinib plus sintilimab (PR, PFS 8.5 months) and, after progression, seventh-line chidamide plus sintilimab plus bevacizumab (SD, PFS 5.5 months). No grade 3–4 AEs occurred. Conclusion This retrospective two-patient case series observed one PR and one SD in heavily pretreated MSS mCRC patients with prior ICI failure who received chidamide plus a PD-1 inhibitor (Case 1: primary resistance; Case 2: acquired resistance). As descriptive observations, these findings are hypothesis-generating only and are insufficient to demonstrate reversal of immunotherapy resistance or survival benefit. Prospective biomarker-driven studies are warranted to evaluate epigenetic-immunotherapy combinations in this subgroup.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.