Hallmarks of cancer

In addition to the description of organ-specific mutations, as was done in the "Multistep Carcinogenesis" model, genetic alterations can also be assigned functional aspects that are essential for neoplastic transformation. They are called Hallmarks of Cancer (Hanahan and Weinberg, 2000; Hanahan and Weinberg, 2011).

According to the study, complex changes in the genome of cancer cells during cancer development result in 100 indispensable cell physiological properties that characterize the malignant phenotype.

The activation of the signalling pathways is achieved by mutations of the onco- and tumour suppressor genes as well as epigenetic alterations of the genome, as already described in the multistep carcinogenesis model.

The 10 hallmarks of cancer are:

• Insensitivity to growth inhibitors (evading growth suppressors)
• Avoiding immune reactions (avoiding immune destruction)
• Unlimited replication potential (enabling replicative immortality)
• Stimulating inflammation (tumor promoting inflammation)
• Tissue invasion and metastasis
• Continuous angiogenesis (inducing angiogenesis)
• Genomic instability and mutation
• Apoptosis (resisting cell death)
• Deregulation of cellular energy control (deregulation cellular energetics)
• Proliferation (sustaining proliferative signaling)

It is remarkable that the importance of the individual cell functions varies between tumours. It is important that each function is characterised by differentiated genes, gene groups or signalling pathways.

Furthermore, the "Hallmarks of cancer" contain properties that do not only result from the tumor cells themselves, but are characterized by a tumor cell stroma(cells) or tumor/microenvironment interaction.

These properties include, for example, inflammatory changes (inflammation). Thus, tumor growth and metastasis cannot be explained as solistic endogenous properties of tumor cells. Rather, tumor formations consist of complex systems consisting of tumor cells themselves, normal cells (e.g., fibroblasts, macrophages, lymphocytes, granulocytes, and endothelial cells), and extracellular matrix (ECM) (Hanahan and Weinberg, 2000). The last two components are combined as stroma.

The ECM consists of solid components, such as collagen, fibronectin, vimentin, and growth signals produced by the cellular component. The tumor cells and the stroma form a complex interaction unit, which moreover cannot be easily simulated in vitro. Only those tumor cells that have the ability to interact with the stroma cells and stimulate them to produce growth factors are capable of tumor proliferation. If, for example, primary malignant tumour cells are isolated from the microenvironment, they are often no longer capable of tumour progression. This also means that tumour cells that are able to grow in vitro without a stroma are a special subselection of tumour cells that may no longer have all the properties of regulation in particular.

1. Hanahan D, Vineyard RA (2000) The Hallmarks of Cancer. Cell, 100: 57-70
2. Hanahan D, Vineyard RA (2011) Hallmarks of Cancer: the next generation. Cell, 144: 646674