Tumour heterogeneity

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Tumour Heterogeneity

Diagram illustrating cancer stem cell model versus stochastic model of tumour heterogeneity.

Tumour heterogeneity refers to the existence of distinct subpopulations of cells within a tumour, which can differ in their genetic, phenotypic, and behavioural characteristics. This diversity within a tumour can have significant implications for cancer diagnosis, treatment, and prognosis.

Types of Heterogeneity

Tumour heterogeneity can be broadly classified into two types: intertumoural heterogeneity and intratumoural heterogeneity.

Intertumoural Heterogeneity

Intertumoural heterogeneity refers to the differences between tumours in different patients. These differences can arise due to variations in genetic mutations, environmental factors, and the tumour microenvironment.

Intratumoural Heterogeneity

Intratumoural heterogeneity describes the diversity of cancer cells within a single tumour. This can result from genetic mutations, epigenetic changes, and differences in the tumour microenvironment. Intratumoural heterogeneity is a major challenge for effective cancer treatment, as different subpopulations of cells may respond differently to therapies.

Models of Tumour Heterogeneity

Linear versus branched evolution models of tumour heterogeneity.

There are several models that attempt to explain the development of tumour heterogeneity:

Cancer Stem Cell Model

The cancer stem cell (CSC) model suggests that a subset of cancer cells, known as cancer stem cells, are responsible for tumour growth and heterogeneity. These cells have the ability to self-renew and differentiate into various cell types within the tumour.

Stochastic Model

The stochastic model proposes that all cancer cells have the potential to contribute to tumour growth and heterogeneity, with differences arising from random mutations and environmental influences.

Evolutionary Models

Tumour evolution can be described by linear or branched models. In the linear model, mutations accumulate sequentially, while in the branched model, different subclones evolve independently, leading to a more complex pattern of heterogeneity.

Implications for Treatment

Illustration of treatment bottleneck due to tumour heterogeneity.

Tumour heterogeneity poses significant challenges for cancer treatment. The presence of diverse subpopulations within a tumour can lead to treatment resistance, as some cells may survive and repopulate the tumour after therapy. Understanding and targeting tumour heterogeneity is crucial for developing more effective treatment strategies.

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References


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Contributors: Prab R. Tumpati, MD