DSTYK Inhibition Sensitizes Non-Small Cell Lung Cancer To Taxane-Based Chemotherapy.

Chemotherapy continues to be the standard treatment for patients non-eligible to targeted or immune-based therapies; however, treatment resistance remains a major clinical challenge. We previously found that expression levels of DSTYK, a poorly explored dual serine/threonine and tyrosine kinase frequently amplified in cancer, identifies lung cancer patients exhibiting poor response to immune checkpoint inhibitors and showed that its inhibition sensitizes to immunotherapy. Seeking to explore the potential of DSTYK targeting in additional indications, we investigated the functional relevance and actionability of DSTYK in lung cancer chemoresistance.

miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response.

Locally advanced non-small cell lung cancer (NSCLC) is frequent at diagnosis and requires multimodal treatment approaches. Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for operable locally advanced NSCLC (Stage IIIA). However, the majority of patients are NACT-resistant and show persistent lymph nodal metastases (LNmets) and an adverse outcome.

DSTYK inhibition increases the sensitivity of lung cancer cells to T cell-mediated cytotoxicity.

Lung cancer remains the leading cause of cancer-related death worldwide. We identify DSTYK, a dual serine/threonine and tyrosine non-receptor protein kinase, as a novel actionable target altered in non-small cell lung cancer (NSCLC). We also show DSTYK's association with a lower overall survival (OS) and poorer progression-free survival (PFS) in multiple patient cohorts.