A narrative review of tumor heterogeneity and challenges to tumor drug therapy

Abstract

Objective: To accurately evaluate tumor heterogeneity, make multidimensional diagnosis according to the causes and phenotypes of tumor heterogeneity, and assist in the individualized treatment of tumors.

Background: Tumor heterogeneity is one of the most essential characteristics of malignant tumors. In tumor recurrence, development, and evolution, tumor heterogeneity can lead to the formation of different cell groups with other molecular characteristics. Tumor heterogeneity can be characterized by the uneven distribution of tumor cell subsets of other genes between and within the disease site (spatial heterogeneity) or the time change of cancer cell molecular composition (temporal heterogeneity). The discovery of tumor targeting drugs has dramatically promoted tumor therapy. However, the existence of heterogeneity seriously affects the effect of tumor treatment and the prognosis of patients.

Methods: The literature discussing tumor heterogeneity and its resistance to tumor therapy was broadly searched to analyze tumor heterogeneity as well as the challenges and solutions for gene detection and tumor drug therapy.

Conclusions: Tumor heterogeneity is affected by many factors consist of internal cell factors and cell microenvironment. Tumor heterogeneity greatly hinders effective and individualized tumor treatment. Understanding the fickle of tumors in multiple dimensions and flexibly using a variety of detection methods to capture the changes of tumors can help to improve the design of diagnosis and treatment plans for cancer and benefit millions of patients.

Keywords: Tumor heterogeneity; diagnosis; drug therapy.

Figure 1

Classification of tumor heterogeneity. Temporal heterogeneity means that the initial tumor cells gradually appear multiple subclones with different genetic characteristics (appeared as different colors of cells) under natural evolution or human intervention. Spatial heterogeneity refers to the uneven distribution of tumor cell subpopulations (appeared as different colors of cells) at the primary tumor and metastatic sites.

Figure 2

Timeline of the development of perceptions of tumor heterogeneity (4-10).

Figure 3

The evolution of tumor heterogeneity. With the accumulation of mutations in critical oncogenic and tumor suppressor genes, normal cells can degenerate into malignant cells. As the disease progresses, cancer cells exhibit marked heterogeneity in response to mechanisms such as genomic instability, epigenetic modifications, plastic gene expression, and different microenvironments (appeared as different colors of cells), ultimately leading to heterogeneous tumorigenesis.