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    • AACR 2026

    Integrative Genomic Analysis Reveals Pharmacogenomic Determinants of Chemotherapy Response 

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    Dr Gowhar S. (1Cell.Ai)

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    The Problem With One-Size-Fits-All Chemotherapy 

    Every oncologist knows the reality:-   

    Two patients with the same cancer diagnosis can respond very differently to the same chemotherapy regimen.  

    Some tolerate it well and respond powerfully. Others suffer severe toxicity with minimal benefit. The difference often lies not in the tumour alone, but in the patient’s own pharmacogenomic (PGx) profile:– the genetic variations that determine how their body metabolises chemotherapeutic agents. 

    At 1Cell.ai, we believe that understanding a patient’s PGx profile before treatment begins is not optional: it is essential. This study demonstrates exactly why. 

    Our Study 

    Using our OncoIndx® NGS panel for comprehensive genomic profiling (CGP), we retrospectively investigated pharmacogenomic markers in 124 cancer patients across a broad spectrum of tumour types including breast, colon, lung, melanoma, pancreatic, stomach, ovarian, rectal, and hepatobiliary cancers. Our study also included a significant cohort from the Uzbek population, reflecting our commitment to expanding precision oncology beyond traditionally studied populations. 

    What We Found 

    The findings were striking. Three critical PGx markers emerged from our analysis: 

    • 92% of patients (n=114) had the DPYD wildtype genotype, associated with reduced risk of adverse events when treated with 5-FU/fluoropyrimidine-based chemotherapy 
    • 2.4% of patients (n=3) carried the DPYD c.1129-5923C (HapB3) variant :- a finding that predicts increased toxicity at standard dosing levels, warranting dose modification before treatment begins 
    • 4% of patients carried wildtype TYMS genotype, and 4.8% (n=6) were identified with a 6bp deletion associated with increased toxicity and adverse drug reactions 
    • 9.7% (n=12) were detected with UGT1A1 wildtype, a critical determinant of response to irinotecan-based chemotherapy 

    Additionally, our analysis identified the DPYD IVS14+1G>A splice-site variant in a significant fraction of the Uzbek population; a finding with major implications for pre-treatment DPD-related 5-FU risk assessment in this underserved patient group. 

    Why This Matters 

    Chemotherapy toxicity is one of the most preventable sources of patient harm in oncology and yet it remains widespread, largely because PGx profiling is not systematically integrated into treatment planning.  

    Our study demonstrates that our CGP assay can reliably identify patients at risk of severe toxicity before treatment begins enabling oncologists to modify dosing, switch regimens, or prepare appropriate supportive care. 

    This is precision oncology in its most direct form; using genomic data to protect patients, not just treat tumours. 

    Presented at the AACR Annual Meeting 2026, San Diego, CA | April 17–22, 2026 | #AACR26 
    Presented by Dr. Gowhar Shafi et al | April 20, 2026 | Session PO.ET07.02

    Read Abstract 

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