Researchers at the University of California, San Francisco (UCSF) have made significant strides in developing a novel humanized antibody-drug conjugate (ADC) targeting the Wnt2 protein for the treatment of lung cancer and other Wnt-driven tumors. Preclinical studies have demonstrated significant anti-tumor effects of the anti-Wnt2-ADC in vitro and in vivo, paving the way for a Phase I clinical trial expected to commence in the near future.
The UCSF Thoracic Oncology Program, led by the Jablons' lab, has been investigating the role of Wnt signaling in thoracic malignancies. Their research has shown that aberrant Wnt signaling, particularly through overexpression of Dishevelled (Dvl) proteins, contributes to the development of lung cancer and mesothelioma. The lab also discovered the critical survival role of Wnt protein ligands as a survival mechanism in these cancers.
Targeting Wnt Signaling with Anti-Wnt2-ADC
To disrupt Wnt signaling, the researchers developed a monoclonal antibody targeting both Wnt-1 and Wnt-2 genes, which induced apoptosis in cancer cells. Building on this work, they created a novel humanized anti-Wnt2-ADC. This ADC has shown promising anti-tumor activity against Wnt-driven tumors, including lung cancer, mesothelioma, and pancreatic cancer, in preclinical models.
The Wnt signaling pathway is crucial in embryonic development and tissue homeostasis, but its aberrant activation is implicated in various cancers. By specifically targeting Wnt2, a key ligand in this pathway, the anti-Wnt2-ADC aims to selectively eliminate cancer cells while minimizing off-target effects.
Molecular Assay for Early-Stage Lung Cancer
In addition to the anti-Wnt2-ADC, the Jablons' lab has developed a 14-gene molecular assay to identify aggressive biology in early-stage non-small cell lung cancer (NSCLC), specifically adenocarcinoma, and predict prognosis. This assay is currently being tested in a prospective, international, randomized Phase III clinical trial and is already CMS (Medicare) approved and reimbursed as a CLIA assay.
The assay helps predict and guide adjuvant therapy for patients with molecularly stratified tumors of intermediate and high risk. According to UCSF, the assay has already benefited thousands of early-stage NSCLC patients and is expected to save tens of thousands more each year once fully approved in clinical guidelines upon completion of the international Phase III trial.
The development of the anti-Wnt2-ADC and the 14-gene molecular assay represent significant advancements in the treatment and management of lung cancer, offering new hope for patients with this deadly disease.
