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Updated: Mar 14, 2026

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
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Targeting cancer metabolism by simultaneously disrupting parallel nutrient access pathways.

Seong M Kim, Saurabh G Roy, Bin Chen

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    A novel synthetic sphingolipid, SH-BC-893, effectively targets cancer by blocking nutrient uptake and internal recycling. This dual action starves cancer cells, offering a promising, selective therapeutic strategy against diverse tumor types.

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    Area of Science:

    • Oncology
    • Molecular Biology
    • Drug Discovery

    Background:

    • Cancer cells rely on anabolic metabolism and nutrient influx via transporters, macropinocytosis, and autophagy.
    • Sphingolipids can suppress tumor growth, but cancer cells utilize parallel nutrient pathways for survival.
    • Targeting these parallel nutrient pathways offers a potential therapeutic strategy for cancer starvation.

    Purpose of the Study:

    • To investigate the efficacy of a synthetic sphingolipid, SH-BC-893, as a dual-action agent against cancer.
    • To elucidate the molecular mechanisms by which SH-BC-893 inhibits nutrient access in cancer cells.
    • To evaluate the selective toxicity of SH-BC-893 against various cancer models and normal tissues.

    Main Methods:

    • Administration of water-soluble, orally bioavailable synthetic sphingolipid SH-BC-893.
    • Assessing nutrient transporter internalization and lysosome-dependent nutrient generation.
    • Investigating the activation of protein phosphatase 2A (PP2A) and mislocalization of PIKfyve and PI(3,5)P2.
    • Evaluating cancer cell killing in vitro and in vivo, including Ras-driven and PTEN-deficient tumors.
    • Assessing the impact on normal proliferative tissues.

    Main Results:

    • SH-BC-893 induced nutrient transporter internalization and blocked lysosomal degradation pathways.
    • The drug activated PP2A, leading to PIKfyve mislocalization and PI(3,5)P2 reduction, causing cytosolic vacuolation and blocking lysosomal fusion.
    • SH-BC-893 selectively killed Ras-driven cancer cells and PTEN-deficient prostate tumors.
    • Normal tissues were unaffected at doses that inhibited tumor growth.

    Conclusions:

    • Simultaneous blockade of parallel nutrient access pathways with SH-BC-893 is a broadly effective and cancer-selective strategy.
    • Sphingolipid-based drugs offer a potential approach to overcome therapeutic resistance driven by tumor heterogeneity.
    • SH-BC-893 demonstrates significant anti-tumor activity with minimal toxicity to normal tissues.