No abstract

GISTs are the most common mesenchymal neoplasms of the gastrointestinal tract. The last 20 years have been revolutionary in the understanding of these tumours and began with the discovery of c-KIT, a proto oncogene that when mutated forms the molecular basis for the growth and development of these malignancies. Surgery was previously considered to be the only treatment modality in both local and advanced disease, however, the introduction of immunotherapy agents such as tyrosine kinase inhibitors has had profound effects on how we now approach and manage these tumours. These novel agents have significantly reduced the frequency of disease recurrence and dramatically improved survival, and serve as a model for the study of targeted therapies in other solid tumors. We present a review of gastrointestinal stromal tumours and consider the current evidence based detection and management of these unique tumors.

No abstract

The development of immune checkpoint inhibitors (ICI) represents a major milestone in immune‐oncology. Over the years these agents have demonstrated efficacy in an increasing array of malignancies. Despite this success however, significant challenges remain. Novel approaches to both drug development and trial design are required to incorporate the unique pharmacokinetic and pharmacodynamic properties of ICIs. Further, it has also been established that the benefit of ICIs is limited to only a subset of patients. The molecular interactions between native immune cells and tumorigenesis and progression represent an active area of biomarker research, and elucidating the mechanisms of response and resistance is crucial to develop rational trial designs for the next wave of immune‐oncology (IO) clinical trials, particularly in patients with primary and/or acquired resistance. Efforts are now being made to integrate both biological and clinical information using novel multi‐omic approaches which are now being developed to further elucidate the molecular signatures associated with IO treatment response and resistance and enable rational drug development and trial design processes. As such, precision IO and the ability to deliver patient‐specific choices for ICI monotherapies or combination therapies has become an increasingly tangible goal. We herein describe the current landscape in ICI drug development and discuss the challenges and future directions in this exciting and evolving era in immune‐oncology.