Annual Review of Cancer Biology - Volume 8, 2024

Cancer research seeks to understand the biology underlying the progression to malignant transformation. Recently, the incidence of esophageal adenocarcinoma (EAC) has increased dramatically, and if we understand why and how, we will be better equipped for diagnosis, prognosis, detection, prevention, and intervention. The earliest steps in progression for most malignancies are the most difficult to study. The initiation of cancer is believed to be a relatively rare and sporadic event, the locations and timings of which are most often unknown. Of the trillions of somatic cells in our bodies, only a few ever find themselves on a path to malignancy. However, chronic inflammation generates a metaplastic lesion that is directly linked to increased incidence of EAC and thus alerts us to the time and place that progression is initiated and allows us to study the biology. We describe recent studies that identify coordinated actions between stromal and epithelial cells that progress to EAC.

The intestinal microbiota, a complex ecosystem of microorganisms, has emerged as an important player in modulating various aspects of human health and disease. The microbiota is in a state of constant cross talk with itself and its host, and these interactions regulate several aspects of host homeostasis, including immune responses. Studies have demonstrated a relationship between the microbiota and outcomes of several cancer immunotherapies. This review explores the different roles of intestinal microbiota in shaping the efficacy and safety of cancer immunotherapies, including allogeneic hematopoietic cell transplantation, immune checkpoint blockade, and CAR T cell therapy.

Our understanding of cancer genomes has allowed for the integration of molecular data into histopathological classifications for routine stratification of patients. In the last 10–15 years, thanks to this systematic implementation of large-scale sequencing, the identification of hotspot somatic mutations in histone genes came into the limelight, underscoring the concept of oncohistones. As drivers in pediatric brain tumors, and in several other types of cancers, oncohistones brought a “new dimension of Strange” into the cancer multiverse, to paraphrase Marvel. An integrative approach to cancer complexity as a multidimensional projection is urgently needed to consider all relevant etiological, developmental, and evolutionary components. Here, we discuss recent progress on histone variants and chaperones, their regulation and alterations in cancers, the available in vivo models, and current treatment strategies. More specifically, we adopt a view through the lens of tissue-specific differences and means for genome expression and integrity maintenance.