HER2 and PD-L1 Expression in Gastric and Gastroesophageal Junction Cancer: Insights for Combinatorial Targeting Approaches.

Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.

KRAS as a Modulator of the Inflammatory Tumor Microenvironment: Therapeutic Implications.

KRAS mutations are one of the most frequent oncogenic mutations of all human cancers, being more prevalent in pancreatic, colorectal, and lung cancers. Intensive efforts have been encouraged in order to understand the effect of KRAS mutations, not only on tumor cells but also on the dynamic network composed by the tumor microenvironment (TME). The relevance of the TME in cancer biology has been increasing due to its impact on the modulation of cancer cell activities, which can dictate the success of tumor progression. Here, we aimed to clarify the pro- and anti-inflammatory role of KRAS mutations over the TME, detailing the context and the signaling pathways involved. In this review, we expect to open new avenues for investigating the potential of KRAS mutations on inflammatory TME modulation, opening a different vision of therapeutic combined approaches to overcome KRAS-associated therapy inefficacy and resistance in cancer.

O papel das mucinas gástricas na infecção por Helicobacter pylori / The role of gastric mucins in Helicobacter pylori infection

Mucinas são glicoproteínas, agentes protetores de mucosas e potenciais moléculas de adesão para microrganismo. A bactéria H. Pylori coloniza o muco gástrico e adere-se ao epitélio por meio de adesinas que reconhecem receptores nas células superficiais. As interações de adesina-receptor contribuem para a cronicidade na infecção, que está associada à patogênese de gastrite, doença péptica e câncer gástrico. MUC5AC e MUC6 são mucinas secretadas respectivamente no epitélio superficial/foveolar e nas glândulas da mucosa gástrica. MUC5AC vem sendo apontada como molécula receptora de H. Pylori, enquanto para MUC6 é atribuído papel na defesa contra o microrganismo. O conhecimento da expressão dessas mucinas na mucosa gástrica infectada por H. Pylori pode contribuir para a compreensão de aspectos de adesão e patogênese da infecção H. Pylori.