Tumor heterogeneity in retinoblastoma: a literature review

Abstract

Tumor heterogeneity, characterized by the presence of diverse cell populations within a tumor, is a key feature of the complex nature of cancer. This diversity arises from the emergence of cells with varying genomic, epigenetic, transcriptomic, and phenotypic profiles over the course of the disease. Host factors and the tumor microenvironment play crucial roles in driving both inter-patient and intra-patient heterogeneity. These diverse cell populations can exhibit different behaviors, such as varying rates of proliferation, responses to treatment, and potential for metastasis. Both inter-patient heterogeneity and intra-patient heterogeneity pose significant challenges to cancer therapeutics and management. In retinoblastoma, while heterogeneity at the clinical presentation level has been recognized for some time, recent attention has shifted towards understanding the underlying cellular heterogeneity. This review primarily focuses on retinoblastoma heterogeneity and its implications for therapeutic strategies and disease management, emphasizing the need for further research and exploration in this complex and challenging area.

Keywords: Cancer complexity; Cellular heterogeneity; Retinoblastoma; Tumor heterogeneity; Tumor microenvironment.

Fig. 1

Schematic representation of the different types of heterogeneity in retinoblastoma (RB): Inter-patient heterogeneity arises from differences in sporadic and hereditary RB cases and is further compounded by variations in high- and low-risk histopathologic features, which may be present even within the same ICRB grouping, thereby influencing treatment response and prognosis. Intra-patient heterogeneity reflects differences between primary and metastatic tumor sites, which may exhibit distinct tumorigenic characteristics. Intra-tumor heterogeneity is shaped by the presence of cancer stem cells and multiple potential cells of origin for RB. These variations are driven by molecular heterogeneity, encompassing diverse genetic, epigenetic, transcriptomic, and metabolomic alterations, which collectively contribute to heterogenous RB progression

Fig. 2

Chronological overview of pivotal discoveries that expanded our knowledge of tumor heterogeneity in retinoblastoma (RB): Key milestones encompass genetic, epigenetic, and transcriptomic alterations, the identification of MYCN-amplified RB subsets, and the involvement of cancer stem-like cells. Advancements in molecular profiling, single-cell transcriptomics, and liquid biopsy methodologies underscore the evolving landscape of RB heterogeneity