The best way to learn about cancer is to understand the mechanisms of cellular control that are altered when a normal cell is transformed into a cancer cell. We have given an overview of this on our What Is Cancer and What Are Cancer Cells pages.
The table below summarizes the mutations that cause a normal cell to be transformed into a cancer cell.
The references from which this information was summarized are given at the bottom of this webpage.
To help you Learn About Cancer we have excepted and adapted a hypothetical journey of a normal lung cell into metastatic lung cancer. This story is a composite of information taken from the references at the bottom of this page, especially from page 338 of “The Emperor of All Maladies – A Biography of Cancer”.
A good way to Learn About Cancer is to capture, simplify and integrate all the information given in the table above by incorporating all the mutation driven cellular modifications into a narrative of a hypothetical journey of a cancer cell as it acquires the hallmarks of a cancer cell. This will help you to truly understand and internalize how a normal cell becomes a cancer cell and how a cancer cell eventually becomes metastatic cancer
We begin our journey with one normal lung cell in lung of a 40-year-old Fire-Safety-Equipment worker. One morning in 1968 a small sliver of asbestos floated into the air, was inhaled by the worker and lodged in the lung near the normal lung cell. The worker’s body reacts to the asbestos sliver with an inflammation. Cells around the sliver begin to divide furiously like a small wound trying to heal. A small clump of normal lung cells (daughter cells of the original normal lung cell) arises at the site of the inflammation.
At some time before the inflammation subsides a random mutation occurs in one cell of that clump. The mutation is in a specific dormant oncogene (cancer-initiating gene). This mutation creates an activated version of the oncogene which causes the mutated cell to grow more swiftly than its neighbors creating a clump of mutated sister cells within the original clump of lung cells. These cells are not yet fully active cancer cell, but are cells in which the one of the normal controls on cell division has partially been removed thus creating cancer’s primordial ancestor.
A decade passes (1978). The small collection of oncogene-mutated cells continues to proliferate, unnoticed, in the far edge of the lung. The Fire-Safety-Equipment worker, being a smoker, inhales some smoke and one of the carcinogenic chemicals in the cigarette smoke reaches the edge of the lung and contacts the clump of cells containing the mutated-oncogene. One cell in this clump acquires a second mutation caused by the carcinogenic chemical in the cigarette smoke which this time activates a second oncogene which further de-regulates the growth controlling mechanisms normally in place in normal cells causing the double mutant cells and their daughters to grow to an even greater extent.
Another decade passes (1988). Yet another cell in that secondary mass of double mutated cells is caught in the path of an x-ray from a routine diagnostic chest x-ray. This x-ray causes yet a third mutation in the double-mutated cells, this time inactivating a tumor-suppressor gene. This mutation has little immediate effect since this cell possesses a second copy of that gene which is still active. But in the next year (1989), another mutation, this one occurring randomly due to an unrepaired mistake in DNA (gene) synthesis during cell division, inactivates the second copy of the tumor suppressor gene thus creating a growing collection of cells that possess two activated oncogenes and a fully inactive tumor suppressor gene.
Now the fatal march is on. The cells, now with four mutations, begin to out-grow their brethren. Over the next decade, as the cells grow more rapidly and extensively than normal cells they acquire additional mutations which activate pathways resulting in cells even further adapted for growth and survival.
One mutation in the tumor allows the cells to avoid signals from crowded neighboring cells to self-destruct (apoptosis) thus avoiding programmed cell death. Another mutation in the small growing tumor allows the cells to incite blood vessels in neighboring vascular cells to grow thus providing blood supply to the rapidly growing tumor cells (angiogenesis). Yet another mutation changes the basic glucose metabolism of the cell and thus allows the tumor to survive even in areas of the body with lower oxygen supply.
Mutant cells beget mutant cells beget mutant cells. Yet another mutation occurs in a gene that inactivates a cell-cell adhesion molecule (CAM) which causes these cells to become untethered or unattached from the tumor itself which allows the mutated cells and daughter cells to migrate from the original tumor site. An additional mutation deregulates the production of proteases (protein hydrolyzing enzymes) which enables the cell to penetrate through surrounding tissue. These cells can now migrate though the lung tissue and enter the blood-stream.
A descendant of this mobile cancer cell through another random mutation acquires the capacity to survive in the bone where it begins yet another cycle of survival, mutation, selection and colonization. This represents the first metastasis of the tumor that originated in the lung.
In 1998, 30 years after the first sliver of asbestos lodged in his lung, the Fire-Safety-Equipment worker noticed he was occasionally short of breath with a twinge of pain at the edge of his chest area. Another year passes, and these breathless episodes and twinges of pain accelerate. The man visits a physician and a CT scan is performed revealing a rind like mass wrapped around a bronchus in the lung. A biopsy reveals lung cancer. A surgeon examines the man and the CT scan of the chest and deems the cancer inoperable. Three weeks after that visit the man returns to the medical clinic complaining of pain in his ribs and hips. A bone scan reveals metastasis to the pelvis and the ribs.
The man soldiers through a punishing regimen of multiple cell-killing chemotherapy drugs The cells in the various detected tumors respond, tumors shrink the worker is declared to be in remission. However, during the chemotherapy, one cell in one of the shrunken tumors acquires yet another mutation that makes it resistant to the most effective drugs being administered in the final round of chemotherapy. During his proclaimed remission, the mutated resistant metastatic cancer cell continues to replicate undetected for a number of years which leads in 2003 to a relapse of his cancer with tumors detected all over his body – in the lungs, the bones, the liver all of which are not resistant to all the standard chemotherapy drugs.
One morning in late 2004, deeply narcotized on opiates in a hospital bed in Boston, surrounded by his wife and children, the man dies of metastatic lung cancer, a sliver of asbestos still lodged in the edge of his lung. He is now 76 years old.
The critical information and conclusions that we believe are important for you to understand and ‘take home’ from the above story include:
As you will read in other pages on our website these hallmark properties of cancer cells not only form the basis for understanding What Cancer Is and What Cancer Cells Are, but also form the basis for developing Customized Treatment and Therapy Protocols for each individual’s cancer. In addition, they also form the basis for the successful treatments chronicled in the Cancer Survivor Stories we share with you on other website pages.
“The Hallmarks of Cancer”, Hanahan, Douglas and Robert A. Weinberg, Cell, v100, 57-100 (2000)
“Hallmarks of Cancer: The Next Generation”, Hanahan, Douglas and Robert A. Weinberg, Cell, v144, 646-674 (2011)
“Designing a Broad-Spectrum Integrated Approach for Cancer Prevention and Treatment”, Block, Keith, et al., Seminars in Cancer Biology, v35, 5276-5304 (2015)
“The Emperor of All Maladies – A Biography of Cancer”, a Pulitzer Prize-winning book by Siddharatha Mukherjeen, MD (2011)