What is cancer(description)
What is cancer?
A few years ago I was at a small meeting with a group of distinguished cancer biologists and clinicians.
It was an interesting meeting because there were also distinguished scientists from other fields. The idea of the meeting was to stimulate cross-fertilization of ideas from different scientific disciplines, with the hope that new paradigms for approaching the causes of cancer and its course would be conceived.
One of the first questions that one of the noncancer researchers asked was, what is the definition of cancer? It was somewhat startling to hear the vigorous discussion and even squabbling among the distinguished cancer scientists in their attempt to define cancer. Although most could agree on a few key characteristics, everyone had
their own caveats or additional variations to add. So, like all good academic groups, they appointed a committee to come up with a consensus definition. As the most gullible person there, I agreed to chair the committee. After many phone calls and E-mails going back and forth, we came up with the definition and more detailed description below. I should note that the definition is the sort of thing that would appear in a dictionary and the description contains some of the points and caveats thought crucial for taking into account the characteristics of this multifaceted disease.
Description
Cancer is a group of diseases of higher multicellular organisms. It is characterized by alterations in the expression of multiple genes, leading to dysregulation of the normal cellular program for cell division and cell differentiation. This results in an imbalance of cell replication and cell death that favors growth of a tumor cell population. The characteristics that delineate a malignant cancer from a benign tumor are the abilities to invade locally, to spread to regional lymph nodes, and to metastasize to distant organs in the body. Clinically, cancer appears to be many different diseases with different phenotypic characteristics. As a cancerous growth progresses, genetic drift in the cell population produces cell heterogeneity in such characteristics as cell antigenicity, invasiveness, metastatic potential, rate of cell proliferation, differentiation state, and response to chemotherapeutic agents. At the molecular level, all cancers have several things in common, which suggests that the ultimate biochemical lesions leading to malignant transformation and progression can be produced by a common but not identical pattern of alterations of gene readout. In general, malignant cancers cause significant morbidity and will be lethal to the host if not treated. Exceptions to this appear to be latent, indolent cancers that may remain clinically undetectable (or in situ), allowing the host to have a standard life expectancy.
Some points in the description may not seem intuitively obvious. For example, cancer doesn't just occur in humans, or just mammals for that matter. Cancer (or at least tumorous growths— these may or may not have been observed to metastasize) has been observed in phyla as old as Cnidaria, which appeared almost 600 million years before the present, and in other ancient phylasuchasEchinodermata(>500millionyears old), Cephalopoda (500 million years old), Amphibia (300 million years old), and Aves (150 million years old). Curiously, cancer has never been seen (or at least reported) in a number of phyla such as Nematoda, Tradigrada, and Rotifera. It is intriguing to consider that these organisms may have some protective mechanisms that prevent them from getting tumors. If so, it would be important to find out what these mechanisms are.
One thing is clear, though, which is that cancer is a disease of multicellular organisms. This trait implies that there is something inherent in the ability of cells to proliferate in clumps or to differentiate into different cell types and move around in the body to sites of organogenesis that is key to the process of tumorigenesis. Problems occur when these processes become dysregulated.
One might also argue that evolution itself has played some tricks on us because some of the properties selected for may themselves be processes that cancer cells use to become invasive and metastatic. Or to phrase it differently: Is cancer an inevitable result of a complex evolutionary process that has advantages and disadvantages? Some of these processes might be the following:
1. The mechanism of cell invasiveness that allows the implantation of the early embryo into the uterine wall and the development of a placenta.
2. Cell motility that allows neural cells, for example, to migrate from the original neural crest to form the nervous system.
3. The development of a large, complex genome of up to 40,000 genes that must be replicated perfectly every time a cell divides.
4. The large number of cells in a human or higher mammal that must replicate and differentiate nearly perfectly every time (some can be destroyed if they become abnormal).
5. The long life span of humans and higher mammals, increasing the chance for a genetic ‘‘hit'' to occur and lead a cell down a malignant path.
As we shall see in later chapters of this book, cancer cells take advantage of a number of these events and processes.
Other questions that arose at the gathering above from scientists not in the field of cancer were the following:
1. Is there a single trait or traits that all cancer cells have?
2. How many genetic ‘‘hits'' does it take to make a cancer cell?
3. What kinds of genes are involved in these hits?
These questions are all dealt with in later chapters. Suffice it to say here that for a cell to become cancerous or at least take the first steps to becoming cancerous, at least two genetic hits are required. One may be inherited and another accrued after birth or both may be accrued after birth (so-called somatic, or spontaneous, hits). The kinds of genes involved are oncogenes, which when activated lead to dysregulated cell proliferation, and tumor suppressor genes, which become inactivated or deleted, producing a loss of the cell's checks and balances controlling cell proliferation and differentiation.
The single most common, if not universal, trait that occurs in all cancers is genetic drift. or the ability of cells to lose the stringent requirement for preciseDNA replication and to acquire the ability to undergo sequential progressive changes in their genome, through mutations, gene rearrangement, or gene deletion. This has sometimes been called the acquisition of a ‘‘mutator phenotype.''
A few years ago I was at a small meeting with a group of distinguished cancer biologists and clinicians.
It was an interesting meeting because there were also distinguished scientists from other fields. The idea of the meeting was to stimulate cross-fertilization of ideas from different scientific disciplines, with the hope that new paradigms for approaching the causes of cancer and its course would be conceived.
One of the first questions that one of the noncancer researchers asked was, what is the definition of cancer? It was somewhat startling to hear the vigorous discussion and even squabbling among the distinguished cancer scientists in their attempt to define cancer. Although most could agree on a few key characteristics, everyone had
their own caveats or additional variations to add. So, like all good academic groups, they appointed a committee to come up with a consensus definition. As the most gullible person there, I agreed to chair the committee. After many phone calls and E-mails going back and forth, we came up with the definition and more detailed description below. I should note that the definition is the sort of thing that would appear in a dictionary and the description contains some of the points and caveats thought crucial for taking into account the characteristics of this multifaceted disease.
Description
Cancer is a group of diseases of higher multicellular organisms. It is characterized by alterations in the expression of multiple genes, leading to dysregulation of the normal cellular program for cell division and cell differentiation. This results in an imbalance of cell replication and cell death that favors growth of a tumor cell population. The characteristics that delineate a malignant cancer from a benign tumor are the abilities to invade locally, to spread to regional lymph nodes, and to metastasize to distant organs in the body. Clinically, cancer appears to be many different diseases with different phenotypic characteristics. As a cancerous growth progresses, genetic drift in the cell population produces cell heterogeneity in such characteristics as cell antigenicity, invasiveness, metastatic potential, rate of cell proliferation, differentiation state, and response to chemotherapeutic agents. At the molecular level, all cancers have several things in common, which suggests that the ultimate biochemical lesions leading to malignant transformation and progression can be produced by a common but not identical pattern of alterations of gene readout. In general, malignant cancers cause significant morbidity and will be lethal to the host if not treated. Exceptions to this appear to be latent, indolent cancers that may remain clinically undetectable (or in situ), allowing the host to have a standard life expectancy.
Some points in the description may not seem intuitively obvious. For example, cancer doesn't just occur in humans, or just mammals for that matter. Cancer (or at least tumorous growths— these may or may not have been observed to metastasize) has been observed in phyla as old as Cnidaria, which appeared almost 600 million years before the present, and in other ancient phylasuchasEchinodermata(>500millionyears old), Cephalopoda (500 million years old), Amphibia (300 million years old), and Aves (150 million years old). Curiously, cancer has never been seen (or at least reported) in a number of phyla such as Nematoda, Tradigrada, and Rotifera. It is intriguing to consider that these organisms may have some protective mechanisms that prevent them from getting tumors. If so, it would be important to find out what these mechanisms are.
One thing is clear, though, which is that cancer is a disease of multicellular organisms. This trait implies that there is something inherent in the ability of cells to proliferate in clumps or to differentiate into different cell types and move around in the body to sites of organogenesis that is key to the process of tumorigenesis. Problems occur when these processes become dysregulated.
One might also argue that evolution itself has played some tricks on us because some of the properties selected for may themselves be processes that cancer cells use to become invasive and metastatic. Or to phrase it differently: Is cancer an inevitable result of a complex evolutionary process that has advantages and disadvantages? Some of these processes might be the following:
1. The mechanism of cell invasiveness that allows the implantation of the early embryo into the uterine wall and the development of a placenta.
2. Cell motility that allows neural cells, for example, to migrate from the original neural crest to form the nervous system.
3. The development of a large, complex genome of up to 40,000 genes that must be replicated perfectly every time a cell divides.
4. The large number of cells in a human or higher mammal that must replicate and differentiate nearly perfectly every time (some can be destroyed if they become abnormal).
5. The long life span of humans and higher mammals, increasing the chance for a genetic ‘‘hit'' to occur and lead a cell down a malignant path.
As we shall see in later chapters of this book, cancer cells take advantage of a number of these events and processes.
Other questions that arose at the gathering above from scientists not in the field of cancer were the following:
1. Is there a single trait or traits that all cancer cells have?
2. How many genetic ‘‘hits'' does it take to make a cancer cell?
3. What kinds of genes are involved in these hits?
These questions are all dealt with in later chapters. Suffice it to say here that for a cell to become cancerous or at least take the first steps to becoming cancerous, at least two genetic hits are required. One may be inherited and another accrued after birth or both may be accrued after birth (so-called somatic, or spontaneous, hits). The kinds of genes involved are oncogenes, which when activated lead to dysregulated cell proliferation, and tumor suppressor genes, which become inactivated or deleted, producing a loss of the cell's checks and balances controlling cell proliferation and differentiation.
The single most common, if not universal, trait that occurs in all cancers is genetic drift. or the ability of cells to lose the stringent requirement for preciseDNA replication and to acquire the ability to undergo sequential progressive changes in their genome, through mutations, gene rearrangement, or gene deletion. This has sometimes been called the acquisition of a ‘‘mutator phenotype.''
