Hallmarks of Cancer: The Next Generation

Cancer quacks frequently exploit the fact that cancer biology is a complex subject. One way to immunize people against cancer quackery is to spread accurate knowledge about cancer. This is exactly what this paper does. It is perhaps one of the best introductory review papers about the biological underpinnings of cancer and its transformation from normal cells to cells that can invade surrounding tissues and spread to other places of the body. It addresses so many different issues and questions.

What role does the immune system play in the surveillance and prevention of tumor formation and spread? What is the tumor microenvironment and why is it so important? Can inflammation promote tumor formation and, if so, how? How can cancer cells survive given substantial genomic instability? What happens with cellular metabolism in tumors and for what benefit does cancer cells deregulate it?

What are cancer stem cells and why is it so crucial to get rid of them? Can cancer cells change into cancer stem cells or vice versa through phenotypic plasticity? What does it mean for tumors to be genetically heterogeneous and what parts of tumors are most diverse? What are some important aspects of signaling interactions during tumor progression?

Hallmarks of Cancer: The Next Generation is a paper on the common fundamental properties of cancer written by Douglas Hanahan and Robert A. Weinberg that was published in the journal Cell in 2011 and can be accessed within their Open Archive program. The authors are well-known in the field and have made substantial research discoveries related to the molecular biology of cancer, such as mice models and discovery of oncogenes (that facilitate cancer) and tumor-suppressor genes (that help prevent cancer).

This paper is perhaps one of the best papers out there to get a basic introduction to cancer biology. It allows you to go from being superficially familiar with the molecular biology underpinnings of cancer and its progression to acquiring a robust overview of the core mechanisms of cancer and the features that make cancer so deadly.

The title of the paper is reminiscent of a previous paper published by the same authors called The Hallmarks of Cancer. It was published in 2000 and was at the time also a welcome review paper for understanding cancer.

Like its predecessor, this later paper covers many of the same topics. However, there are multiple aspects that are entirely new. This later paper includes two new hallmarks of cancer that was not part of the previous review paper.

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The first new hallmark of cancer in this later paper is the ability for cancer to avoid being targeted and destroyed by the immune system. It has been known for a long time that the immune system can attack cancer cells because cancer cells mutate and become so different that the body no longer recognize it as self. However, some molecules on the surface of some cancer cells are still similar enough to ordinary cells in the body, so the immune system cannot always easily discover cancer cells and target them for destruction. Cancer cells also have many sneaky methods of avoiding the different effector cells of the human immune response.

The second new hallmark is changed energy metabolism. It turns out that cancer cells have a somewhat different approach to it than normal cells. Cancer cells lean towards favoring glycolysis over oxidative phosphorylation. These are two different pathways in the human body that generates an energy currency called adenosine triphosphate (ATP) that stores chemical energy that can then be released in other processes that needs it.

It was not entirely clear at the time why cancer cells have this altered metabolism, but one model that was proposed would indicate that the intermediate substances produced during glycolysis can be used in other importance processes that boost the ability of the cancer to make more of itself, such as making more building blocks of DNA and protein.

Besides adding two new emerging hallmarks of cancer, this review paper also take a deeper look into what the authors call “enabling characteristics” of cancer. The two characteristics that are given the most space is genome instability and tumor-promoting inflammation. Why is genome instability important? Many cancer cells have undergone mutations in the system that is involved in DNA repair.

This prevents the standard DNA repair processes of the cell to repair the damage caused by mutations and stop the progression to cancer. As the DNA repair system no longer works to the same degree, even more damage to the genome can occur without being repaired over time. Instead, it is not uncommon for cancer cells to gain or lose copies of genes.

What is tumor-promoting inflammation? In the past, a lot of space has been given to the fact that there are things like radiation and chemicals that can cause mutations in these cells. As these accumulate, it can cause cancer. But what was become increasingly obvious over the last few decades is that inflammation can also play an important factor in the development of cancer.

Now, inflammation has nothing to do with how the term is being used by some pseudoscientific quacks that push “inflammation” as the cause of virtually all diseases. The immune system is not just a threat to cancer, but can actively help it. When the area around a developing tumor becomes inflamed, cells from the immune cell move into the neighborhood. Some might attack the tumor, but others can produce helpful molecules (such as growth factors) that alters the tumor microenvironment in such a way as to benefit the tumor.

More indirectly, some cells in the immune system produces corrosive molecules called reactive oxygen species that can increase mutation rate of the cells of the cancer. More mutations means more ways towards tumor progression, since the microevolution process of cancer cells is very hard.

The paper is available both online and in PDF format. A cached version of the online paper can be found here. There is no cache available for the PDF version of the paper at this time.

Emil Karlsson

Debunker of pseudoscience.

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