For resectable esophageal cancer, the current standard of care includes chemoradiation to reduce the tumor size, followed by surgery. Although this therapy has improved treatment outcomes for this disease, its prognosis remains dismal.
The groups of Maarten Bijlsma and Hanneke van Laarhoven study the mechanisms that drive esophageal cancer resistance to treatments. They found that a collective of non-cancerous cells in the tumor known as ‘the stroma’ contributes to therapy resistance. Specifically, it was found that secretion of a signaling molecule, interleukin-6 (IL-6), by certain stromal cells conferred resistance to pre-surgery chemoradiation therapy. Exposure to IL-6 triggered a transformation of the esophageal cancer cells into a chemoradiation resistant tumor cell state.
In parallel, the researchers developed a diagnostic test to monitor IL-6 producing cancer-associated stromal cells using a specific marker (ADAM12) that is detectable the in bloodstream. This test can be used to predict which patients have chemoradiation therapy-resistant esophageal cancer cells. In addition, the researchers suggested that available medication targeting IL-6 signaling may prove helpful in treating chemoradiation-resistant esophageal cancer (Ebbing et al. PNAS 2019).
Spurred by these biological insights, the availability of a diagnostic test and clinically approved medication to block IL-6 signaling, a clinical trial was proposed. With financing by Oncode, this has culminated in the design and request for ethical approval of the clinical trial BASALT: Blood-borne Assessments of StromAL activation to guide Therapy in gastrointestinal cancers. In this phase II trial, patients with resectable adenocarcinoma of the esophagus will be stratified based on ADAM12 levels in a blood sample and assigned to receive control chemoradiation, or chemoradiation with an IL-6 blocker.
This highly efficient and fast translation of research to clinical testing exemplifies the power of the multidisciplinary collaborations at CCA. We believe that our multidisciplinary and concerted approach is essential in paving the way to groundbreaking discoveries in cancer research and the rapid translation of these findings into effective cancer treatments.