Validation of the use of a fluorescent PARP1 inhibitor for the detection of oral, oropharyngeal and oesophageal epithelial cancers.

For oral, oropharyngeal and oesophageal cancer, the early detection of tumours and of residual tumour after surgery are prognostic factors of recurrence rates and patient survival. Here, we report the validation, in animal models and a human, of the use of a previously described fluorescently labelled small-molecule inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) for the detection of cancers of the oral cavity, pharynx and oesophagus. We show that the fluorescent contrast agent can be used to quantify the expression levels of PARP1 and to detect oral, oropharyngeal and oesophageal tumours in mice, pigs and fresh human biospecimens when delivered topically or intravenously. The fluorescent PARP1 inhibitor can also detect oral carcinoma in a patient when applied as a mouthwash, and discriminate between fresh biopsied samples of the oral tumour and the surgical resection margin with more than 95% sensitivity and specificity. The PARP1 inhibitor could serve as the basis of a rapid and sensitive assay for the early detection and for the surgical-margin assessment of epithelial cancers of the upper intestinal tract.

The evolving role of immuno-oncology for the treatment of head and neck cancer.

Monoclonal antibodies (mAbs) that target immune co-signaling pathways have the potential to enable immune mediated tumor eradication. While early adoption of these agents for the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN) has produced some astounding clinical successes, the majority of patients fail to respond to therapy. The purpose of this review is to first provide a broad overview of the immuno-oncology (I-O) landscape and to then focus on the current status of mAb-based I-O (mAb:I-O) for the treatment of SCCHN, with particular attention to the development of strategies for improving treatment responses.