Gene fusions are important, and often targetable, drivers of the development, progression, and survival of cancer. This article will:

• Provide a brief historical overview of how fusions were initially identified as oncogenic drivers
• Examine the chromosomal basis of gene fusions        
• Describe the mechanisms by which gene fusions are detected

NTRK gene fusions have been found in a broad range of tumor types, but until recently have had no approved targeted treatment. This article will:

• Provide a comprehensive review of the NTRK family and the structure and function of both normal TRK proteins and fusions found in cancer
• Examine the key cancer types in which these fusions are found

ROS1 fusions are an established target of therapy in non-small cell lung cancer. This article will:

• Review the normal structure/function of ROS1
• Examine the role of ROS1 fusions in cancer

Entrectinib targets a number of fusions, including those involving NTRK and ROS1. This article will:

• Discuss the mechanism of action of entrectinib
• Review key clinical data for entrectinib

A number of agents, both newer and well-established, are approved for the management of tumors driven by NTRK and ROS1 fusions. This article will review the data for 4 key competitors:

• Larotrectinib, a kinase inhibitor that inhibits NTRK
• Crizotinib, a ROS1 inhibitor
• Ceritinib, a ROS1 inhibitor
• Lorlatinib, a ROS1 inhibitor