Highlights of This Issue

Abstract

Inflammation is a key driver of oncogenesis. Using complimentary in vitro and in vivo studies, Ayers and colleagues identify a role for potent pro-inflammatory mast cells (MCs) in inflammatory-driven Kaposi Sarcoma (KS). MCs are closely associated with spindle cells, extensively activated to degranulate, and infected by KSHV in patient tumors. Patients display signs of extensive MC activation, including elevated plasma levels of histamine and tryptase. Successful treatment of an AIDS-KS patient with anti-MC therapy underscored their clinical importance. These data strongly suggest a specific role for MCs in KSHV-driven oncogenesis and identify MC antagonists as a promising novel, pathogenesis-targeted, therapeutic approach to KS.Crohn's disease (CD) can form precursor lesions, which harbor a risk to becoming colorectal cancer (CRC). The distinction of these precursors from sporadic adenoma or non-neoplastic inflamed mucosa is crucial for proper patient guidance; however, histology and endoscopy are unreliable and exhibit only low inter-observer agreement. Hirsch and colleagues identified TP53 mutations, aneuploidy and gains of chromosome arm 5p as early and frequent changes in CD to CRC progression. Gains of 5p were a distinctive feature of CD-related carcinogenesis and offer, together with TP53 mutation determination, an easily applicable tool for identifying high risk precursor lesions in CD.Erb-B2 receptor tyrosine kinase 2 (ERBB2) mutations have been identified across a wide range of cancers, but many of the mutations are still variants of unknown significance. Nagano and colleagues comprehensively assessed the transforming activities and drug sensitivities of 55 nonsynonymous ERBB2 mutations using the mixed-all-nominated-in-one (MANO) method. This study identified several ERBB2 mutations as activating mutations that showed varying sensitivities to ERBB2-targeted inhibitors. Thus, the MANO method might be beneficial for the determination of the best treatment for cancers harboring ERBB2 mutations and offer a fundamental database to help customize therapy for ERBB2-driven cancers.Cheung and colleagues demonstrate that the folate transporter and tumor-associated antigen folate receptor alpha (FRα) is overexpressed by aggressive high-grade triple-negative breast cancers (TNBC) and postneoadjuvant chemotherapy residual tumors. FRα is associated with poor clinical outcomes, and it participates in cancer cell signaling and growth through Src and ERK signaling. FRα and the folate cascade could be targeted with specific inhibitor drugs. Both antibody immunotherapy priming Fc-mediated antitumor immune responses, and antibody-drug conjugate treatment delivering a Src pathway inhibitor to FRα-expressing cells, significantly impaired TNBC growth, thus suggesting potential new therapeutic strategies for biological subsets of TNBC with poor prognosis.