Doublecortin-like kinase 1 (DCLK1) (DCLK1)

Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated serine/threonine kinase that serves as a definitive marker for cancer stem cells (CSCs) in various solid tumors, including colorectal and pancreatic cancers (Sureban et al., 2011, PubMed: 21212444). While the long isoform (DCLK1-L) is primarily intracellular and expressed in normal tissues, specific cancer-associated short isoforms (DCLK1-S or ASV) are overexpressed in malignant cells and uniquely exhibit an extracellular domain (ECD) on the cell surface (Weygant et al., 2015, PubMed: 26053294). This tumor-specific surface expression makes the DCLK1-S ECD a highly attractive target for therapeutic interventions such as monoclonal antibodies (e.g., CBT-15) and CAR-T cell therapies, which can selectively eliminate CSCs while sparing normal cells (Westphalen et al., 2014, PubMed: 24441104). DCLK1 signaling is a key driver of the epithelial-mesenchymal transition (EMT) and promotes tumor survival, metastasis, and resistance to chemotherapy (Nakanishi et al., 2013, PubMed: 23292625). Targeting the extracellular domain allows for the delivery of cytotoxic payloads via antibody-drug conjugates (ADCs) or direct immune-mediated destruction of the tumor-initiating cell population.

Other names

DCAMKL1Doublecortin-like and CAM kinase-like 1CLICK-IDCLKDCLK1-SDCLK1-ASVCancer stem cell marker DCLK1

Antibody-mediated targeting of the extracellular domain of the DCLK1-S isoform to induce cell death or deliver payloads; small molecule inhibition of the intracellular kinase domain to disrupt oncogenic signaling pathways.