Enabling Characteristics

In their paper “Hallmarks of Cancer: The Next Generation”, Hanahan and Weinberg (2011) reported that two enabling characteristics underlie the 8 cancer hallmarks they identified.

These enabling characteristics are:

• Genome instability, which generates the genetic diversity that expedites their acquisition, and
• Inflammation, which fosters multiple hallmark functions.

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A high frequency of mutations within a genome leads to genome instability.

As we know cancer develops with an accumulation of mutations where cancer cell possessing mutations that support faster growth, will result in a robust tumor.

The literature is clear that molecular-genetic analysis advancements of cancer cell genomes provided compelling evidence of function-altering mutations and of ongoing genomic instability during tumor progression. While the mutations vary significantly between different tumor types, it is clear that instability of the genome is characteristic of most human cancer cells. 

As such, compromised genome surveillance is instrumental for tumor progression, supporting the acceleration of developing premalignant cells to accumulate favourable genotypes. Genome instability is an enabling characteristic that is described in the hallmark enabling replicative immortality.

During cancer, NFKB is activated in immune cells to ultimately attract more immune cells into the tumor. The main immune cells are the Tumor Associated Macrophages (TAMs) that are found in most malignant tumors, where they can comprise up to 50 percent of the cell tumor mass. TAMs assist cancer cells to bypass some of the anti-cancer defence mechanisms to support tumor growth through four main mechanisms.

• Supply of growth factors (EGF, FGF) and cytokines (IL-6, TNFα) as noted in the hallmark self-sufficiency in growth signals.
• TAMs secrete VEGF AND PDGF into the tumor microenvironment to promote angiogenesis through the hypoxia response pathway as presented in the hallmark sustained angiogenesis. 
• TAMs secrete matrix metalloproteases leading to invasion and metastases described in the hallmark activating invasion and metastasis.
• TAMs support the tumor’s ability to evade the immune system through the production of immunosuppressive molecules that neutralize the immune systems’ ability to kill cancer cells as presented in the hallmark on cancer immunotherapy