Circulating tumor cells (CTCs) are cells that are shed from tumors into the bloodstream. Cell enrichment and isolation technology as well as molecular profiling via next-generation sequencing have allowed for a greater understanding of tumor cancer biology via the interrogation of CTCs. CTC detection can be used to predict cancer relapse, progression, and survival; evaluate treatment effectiveness; and explore the ex vivo functional impact of agents. Detection methods can be by either immunoaffinity (positive or negative enrichment strategies) or biophysical strategies. CTC characterization, which is performed by DNA, RNA, and/or protein techniques, can predict metastatic potential. Currently, CTC-derived explant models may mimic patient response to chemotherapy and help with studying druggable targets and testing treatments. The Food and Drug Administration has cleared a CTC blood test to enumerate CTCs derived from breast, prostate, and colorectal cancers. In conclusion, liquid biopsies via CTCs provide a non-invasive way to obtain important diagnostic, prognostic, and predictive information in patients with cancer.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) axis is implicated in cancer, inflammation, and immunity.Numerous cytokines/growth factors affect JAK/STAT signaling. JAKs noncovalently associate with cytokine receptors, mediate receptor tyrosine phosphorylation, and recruit STAT proteins.Tyrosine-phosphorylated STATs dimerize and are transported into the nucleus to function as transcription factors. Signaling is attenuated by specific suppressor of cytokine signaling proteins, creating a negative feedback loop. Both germline mutations and polymorphisms of JAK family members correlate with specific diseases:systemic lupus erythematosus (TYK2 polymorphisms); severe combined immunodeficiency (JAK3 mutations); pediatric acute lymphoblastic leukemia (TYK2 mutations); and hereditary thrombocytosis (JAK2 mutations). Somatic gain-of-function JAK mutations mainly occur in hematologic malignancies, with the activating JAK2 V617F being a myeloproliferative disorder hallmark; it is also seen in clonal hematopoiesis of indeterminate potential. Several T-cell malignancies, B-cell acute lymphoblastic leukemia, and acute megakaryoblastic leukemia harbor JAK family somatic alterations. JAK2 copy number loss is also associated with immune checkpoint inhibitor resistance.JAK inhibitors (jakinibs) have been deployed in many conditions with JAK activation; they are approved in myeloproliferative disorders, rheumatoid and psoriatic arthritis, atopic dermatitis, ulcerative colitis, graft-versus-host disease, alopecia areata, ankylosing spondylitis, and in patients hospitalized for COVID-19.Clinical trials are investigating jakinibs in multiple other autoimmune/inflammatory conditions.

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