The Hallmarks of Cancer

Cancer quackery is one of the worst forms of pseudoscience. It exploits desperate people who are dying of cancer into buying expensive products that does nothing to treat or cure the cancer. Instead, the quacks increase financial stress. Because alternative medicine is largely unregulated, there is no telling what stuff is really in fake cancer cures. It could make dying people even more sick, robbing them even further of the precious time they have left to spend with friends and family. It can even encourage people with cancer to pick quackery over medicine altogether. It can also infect them with a dangerous anti-medicine ideology.

Many science advocates and scientific skeptics can effectively engage specific fake cancer cures or how to reason about allegedly safe and effective treatments more generally. However, a crucial aspect to fight cancer quackery is knowing more about cancer, including defining features, contributing factors and treatment options. That way science advocates and others can rest their criticism of cancer quackery on a robust foundation consisting of broad knowledge of cancer biology.

There are many different kinds of cancer and there is a huge variation in genotypes within a single kind of cancer. So how can we get a grasp of the complexities of cancer without getting lost in the details? Are there some unifying principles of cancer molecular biology that can be discerned from the data?

How can cancer cells grow even in the absence of external growth stimuli? Why are they immune to anti-growth signals from their environment? How can they avoid programmed cell death? How can they make sure they have a steady supply of nutrients? How can they move through tissue and create daughter tumors in completely different parts of the body? A seminal review paper exploring these issues emphasizes six such key principles.

The Hallmarks of Cancer is a classic review paper on the molecular biology and cell physiology of cancer written by Douglas Hanahan and Robert A. Weinberg and published in the journal Cell in 2000 and is now available as part of their Open Archive initiative. Hanahan and Weinberg are two giants in cancer biology and have both made astonishing contributions to the field. For instance, Hanahan developed transgenic mice models for cancer and Weinberg discovered the first ever oncogene and tumor-suppressor gene. This paper is one of the most highly cited paper in cancer biology of all time, scoring at least 15 000 citations by other papers.

Hallmarks of cancer: what are they?

The general idea behind the paper is that although there are a myriad of different types of cancer and a broad diversity even within specific cancer types, they all share certain common features that the authors labeled “hallmarks of cancer”. The paper highlighted six different hallmarks: limitless replicative potential, sustained angiogenesis, evading apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, and tissue invasion and metastasis.

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Limitless replicative potential means that cancer cells do not go into senescence after they have replicated a certain number of times, but continue indefinitely if enough resources are available. Cells growing in an average cell culture will stop dividing and “become old”. This is because each cell division shortens the telomeres at the end of chromosomes due to the fact that they the very ends of them are not replicated during DNA replication. When they have become short enough, the cells go into senescence. Cancer cells, on the other hand, express the enzyme telomerase that does replicate the ends of the telomeres and are therefore not substantially affected by this problem.

Sustained angiogenesis means that the tumor can make blood vessels grow into it to feed it with oxygen and nutrients. This allows cancer cells to stay alive, mitigate cellular stress and even spread to other parts of the body at a later point.

Evading apoptosis means that the tumor cells have turned off their inner self-destruction system that would have otherwise killed off the cells. What normally happens when a cell is misbehaving is that signals in the body or signals inside the cell order it to go into apoptosis to die and therefore solve the problem. However, in many cancer tumors, this system has suffered mutations that prevents it from being triggered. Most often, the internal apoptosis system is disabled because anti-apoptotic regulators dominate and prevents the cancer cell from going into apoptosis.

Self-sufficiency in growth signals means that the cancer cells are not dependent on external growth signals and can make their own. Normally, a cell requires mitogenic growth signals from the outside to be able to proliferate. Cancer cells, on the other hand, often generate their own growth signals. They are therefore less reliant on external growth signals. Many genes that contribute to cancer (called oncogenes) produce such growth signals.

Insensitivity to anti-growth signals means that the tumor cells do not care if the body tries to tell the tumor cells to stop growing uncontrollably. Tissue invasion and metastasis is the ability of cancer cells to burrow through tissues, enter the bloodstream, enter tissues in other areas of the body and form daughter tumors. Most people who die from cancer die from metastases.

The paper also highlights the impact of genome instability and the fact that there are many pathways to cancer. This is because mutations that enable the above six hallmarks do not have to happen in a specific order. Focusing on the hallmarks of cancer is useful because it offers a productive framework for thinking about the origin and development of cancer.

The paper on the hallmarks of cancer is available both online and in PDF format. A cache of the online version can be found here, but there is no cached version of the PDF file available at this time.