Last reviewed 2026-04-23 · How we verify

ISIS 3521

ISIS 3521 is an antisense oligonucleotide that inhibits protein kinase C-alpha (PKC-alpha) expression to suppress cancer cell proliferation and survival.

ISIS 3521 is an antisense oligonucleotide that inhibits protein kinase C-alpha (PKC-alpha) expression to suppress cancer cell proliferation and survival. Used for Non-small cell lung cancer, Ovarian cancer, Colorectal cancer.

At a glance

Mechanism of action

ISIS 3521 works by binding to and degrading the mRNA encoding protein kinase C-alpha, a signaling enzyme overexpressed in many cancers that promotes cell survival and proliferation. By reducing PKC-alpha levels, the drug aims to induce apoptosis in cancer cells and enhance sensitivity to chemotherapy and radiation. This antisense approach targets a key survival pathway in malignant cells.

Approved indications

• Non-small cell lung cancer
• Ovarian cancer
• Colorectal cancer

Common side effects

• Infusion-related reactions
• Thrombocytopenia
• Nausea and vomiting
• Fatigue

Key clinical trials

• Chemotherapy in Treating Women With Previously Treated Metastatic Breast Cancer (PHASE2)
• Carboplatin and Paclitaxel With or Without ISIS 3521 in Treating Patients With Non-Small Cell Lung Cancer (PHASE3)
• ISIS 3521 in Treating Patients With Advanced, Unresectable, or Metastatic Non-small Cell Lung Cancer or Unresectable or Metastatic Melanoma (PHASE2)
• A Phase 3 Trial of LY900003 Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in Patients With Advanced, Previously Untreated Non-Small Cell Lung Cancer (PHASE3)
• A Phase 2 Trial of Antisense Nucleotide to PKC-Alpha (LY900003, ISIS 3521) Plus Gemcitabine and Carboplatin in Patients With Advanced, Previously Untreated Non-Small Cell Lung Cancer. (PHASE2)

Primary sources

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