Innovative Approaches

Cancer Stem Cells – Key drivers of tumor recurrence and metastasis

Many types of cancer contain rare subpopulations of quiescent cells that are resistant to standard therapy and thought to be key drivers of tumor recurrence and metastasis. These malignant cells are referred to as tumor initiating cells or cancer stem cells (CSCs), because of their capacity to self-renew (clonogenic potential) and form new tumors in non-clinical studies.

Standard chemotherapy and other conventional agents are effective against actively proliferating bulk tumor cells, but do not target CSCs. As a result, after initial responses to standard treatments, tumors may re-grow due to CSC proliferation and differentiation, causing relapse of the disease.

Targeting Cancer Stem Cells

Therapeutics that target CSCs, particularly when combined with conventional debulking agents, may delay or prevent the regrowth of tumors and metastasis formation, potentially increasing the duration of response and progression-free survival (PFS) in patients.

While CSCs have distinct properties from the bulk tumor, both populations share increased telomerase activity, suggesting they may both be susceptible to telomerase inhibition. Numerous preclinical studies using cell culture systems and rodent models of human cancer have shown that Geron’s telomerase inhibitor, imetelstat, is effective at inhibiting growth of tumors from CSCs from a broad range of tumor types through multiple mechanisms including inhibiting growth and inducing differentiation, senescence and apoptosis.

Imetelstat is currently in clinical development as a potential therapeutic agent for the treatment of solid tumors and hematological malignancies. Geron's Phase 2 clinical program includes malignancies in which CSCs are believed to play an important role in disease progression and relapse after standard therapy.