The Hallmarks of Cancer

"The Hallmarks of Cancer" is a seminalpeer-reviewed article published in the journal Cell in January 2000 by the cancer researchers Douglas Hanahan and Robert Weinberg.

The authors believe that the complexity of cancer can be reduced to a small number of underlying principles. The paper argues that all cancers share six common traits ("hallmarks") that govern the transformation of normal cells to cancer (malignant or tumor) cells.

The traits ("hallmarks") that the authors highlight in the paper are (1) Cancer cells stimulate their own growth (self-sufficiency in growth signals); (2) They resist inhibitory signals that might otherwise stop their growth (insensitivity to anti-growth signals); (3) They resist their programmed cell death (evading apoptosis); (4) They can multiply indefinitely (limitless replicative potential) (5) They stimulate the growth of blood vessels to supply nutrients to tumors (sustained angiogenesis); (6) They invade local tissue and spread to distant sites (tissue invasion and metastasis).

By November 2010, the paper had been referenced over 15,000 times by other research papers, and was downloaded 20,000 times a year between 2004 and 2007. As of March 2011, it was Cell's most cited article.

In an update published in 2011 ("Hallmarks of cancer: the next generation"), Weinberg and Hanahan proposed four new hallmarks: (1) abnormal metabolic pathways, (2) evading the immune system, (3) genome instability, and (4) inflammation.

Cancer cells have defects in the control mechanisms that govern how often they divide, and in the feedback systems that regulate these control mechanisms (i.e. defects in homeostasis).

Normal cells grow and divide, but have many controls on that growth. They only grow when stimulated by growth factors. If they are damaged, a molecular brake stops them from dividing until they are repaired. If they can't be repaired, they commit cell suicide (apoptosis). They can only divide a limited number of times. They are part of a tissue structure, and remain where they belong. They need a blood supply to grow.

All these mechanisms must be overcome in order for a cell to develop into a cancer. Each mechanism is controlled by several proteins. A critical protein must malfunction in each of those mechanisms. These proteins become non-functional or malfunctioning when the DNA sequence of their genes is damaged through acquired or somatic mutations (mutations that are not inherited but occur after conception). This occurs in a series of steps, which Hanahan and Weinberg refer to as hallmarks.

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