SHORT DESCRIPTION This incomplete autophagy inducer triggers caspase-mediated apoptosis in cancer cells by inducing incomplete autophagy, leading to tumor reduction and improved survival.
INVENTORS
NU Tech ID: NU 2021-245
IP STATUS
US Patent pending.
DEVELOPMENT STAGE
TRL-5 Prototype Validated in Relevant Environment: Efficacy confirmed in multiple preclinical models demonstrating tumor reduction and enhanced survival.
BACKGROUND Brain metastases are the most common central nervous system malignancy, occurring in an estimated 10–30% of adults with cancer and accounting for the majority of intracranial tumors. They often manifest with neurological impairment that portends poor quality of life and limits survival outcomes. Breast cancer is the most common cancer among women, impacting 2.1 million per year, and it is also the most common cause of cancer related deaths in women, with rates increasing in nearly every region globally. HER2‑positive and triple‑negative breast cancers have particularly high brain metastasis rates, and while novel targeted therapies have improved systemic control and survival in these aggressive forms of cancer, they are limited by high toxicity and poor blood–brain barrier penetration which leads to the emergence or or progression of CNS metastases despite effective extracranial disease control. There is an urgent need for innovative approaches that can more effectively target breast cancer brain metastases (BCBM) while minimizing side effects.
ABSTRACT
Northwestern researchers have developed a therapeutic strategy for cancer, especially breast, lung, melanoma, and primary brain tumors, based on incomplete autophagy induction to trigger caspase‑mediated apoptosis, with a particular focus on repurposing the CNS drug metixene (methixene) and related thioxanthene/piperidine small molecules. Instead of fully blocking or fully activating autophagy, the compounds drive an autophagic process that stalls before completion, leading to cellular stress, and apoptotic cell death in both primary and brain‑metastatic cancer cells while sparing normal tissue. The inventors describe methods of using such agents, including metixene, metixene HCl, and metixene hydrates, via systemic or local delivery and demonstrated significant decreases in cell viability and increased caspase activity in metastatic breast cancer models. In vivo, metixene reduces tumor size and extends survival in preclinical models of both primary breast cancer and brain metastases. The approach leverages modulation of autophagy pathways to induce apoptosis and offers a new avenue for cancer treatment.
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