AI Article Synopsis

  • Lung cancer treatments could be improved using aerosol therapies, but there's a challenge with rapid clearance of drugs from the lungs and undesired systemic effects.* -
  • Researchers found that nebulized AvidinOX can capture biotinylated drugs, significantly enhancing the effectiveness of Cetuximab for treating advanced human lung cancer in mice using much lower doses.* -
  • The therapy showed promising results by blocking crucial signaling pathways in cancer cells, and with good tolerability and available materials, it could quickly move to clinical use.*

Article Abstract

Lung cancer, as well as lung metastases from distal primary tumors, could benefit from aerosol treatment. Unfortunately, because of lung physiology, clearance of nebulized drugs is fast, paralleled by unwanted systemic exposure. Here we report that nebulized AvidinOX can act as an artificial receptor for biotinylated drugs. In nude and SCID mice with advanced human KRAS-mutated A549 metastatic lung cancer, pre-nebulization with AvidinOX enables biotinylated Cetuximab to control tumor growth at a dose lower than 1/25,000 the intravenous effective dose. This result correlates with a striking, specific and unpredictable effect of AvidinOX-anchored biotinylated Cetuximab, as well as Panitumumab, observed on a panel of tumor cell lines, leading to inhibition of dimerization and signalling, blockade of endocytosis, induction of massive lysosomal degradation and abrogation of nuclear translocation of EGFR. Excellent tolerability, together with availability of pharmaceutical-grade AvidinOX and antibodies, will allow rapid clinical translation of the proposed therapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253431PMC
http://dx.doi.org/10.18632/oncotarget.2409DOI Listing

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