Cancer? What's that: Understanding Cancer

Approximately 1 out of every 3 people living in the United States will be diagnosed with some form of cancer in their lifetime. (1)

This is a daunting statistic that invokes feelings of helplessness. Luckily, there is hope. Thousands of physicians, researchers, pharmacologists, government officials, and communities dedicate their time, energy, and resources into tackling this major health issue. However, no one should be confined to the sidelines. Whether a person has received a cancer diagnosis, or knows someone who has, there are meaningful ways to contribute to the solution, and it all begins with understanding cancer at its core.

What is cancer?

Cancer is a group of diseases. Yes, there exist numerous cancer types, all with different prognoses, different molecular features, and therefore different standards of care. However, there are common features or characteristic hallmarks of the disease which make a disease “cancer.” (Figure 1. Hanahan and Weinberg). For normal cells to become cancer, they must find a way to resist cell death.

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Figure 1: Hallmarks of Cancer

However, cancer cells have found ways to evade these normal cell death mechanisms, to sustain proliferative signaling, and totally ignore the growth suppressors encoded into every cell. Once mutant, pre-cancerous cells have acquired these malicious attributes, they must find a way to sustain the life of an ever-growing tumor. These include building their own vasculature to get nutrients and oxygen (angiogenesis). Another method is traveling to more hospitable locations in the body, rather than the primary site of the tumor (invasion and metastasis). Many find ways to constantly replicate their own DNA – which is the basic premise of mitotic division.

So how does this happen?

It starts with the basic dogma of biology. Every cell in our body contains DNA in the genome, which gets transcribed into RNA, which carries the instructions for building proteins that the cell needs to do its specific job. Now, the genes in DNA that get made into RNA and subsequently, protein, vary from different cell types. A cell in your pancreas serves a different function than a cell in your brain, and so, those different cells turn on different genes and utilize different proteins to signal their proper function. Proteins are important signaling molecules in every cell. They are the doers responsible for controlling the pathways just described above. When DNA, RNA, and protein all work together harmoniously, we have healthy cells and a healthy human.

However, harmful stimuli like UV radiation, carcinogens in tobacco smoke, and high-fat diets have all been shown to disrupt normal cellular signaling at the DNA, RNA, or protein levels. On the other hand, some cancers are known to be genetic. Inheritance of mutations in the BRCA1 gene is strongly associated with breast cancer. Any of these cellular insults, whether from lifestyle exposures or genetic lesions, can cause what were once normal, happy cells, to now misbehave and grow uncontrollably.

Since November is pancreatic cancer awareness month, we will use this as our real-life example. A normal pancreatic cell is either supposed to secrete digestive enzymes or release hormones that help regulate our blood sugar, insulin, and glucagon. The growth of these cells is normally controlled within our pancreas to help maintain a healthy, functioning organ. This maintenance is entirely disrupted in pancreatic tumors. By tumor sample DNA sequencing, physicians and researchers have learned that some pancreatic cancer cells have acquired activating mutations in the KRAS gene, among many others. This mutation results in a KRAS protein that is always on, or "consituitively active." This KRAS protein will constantly promote growth signals in these cells. If left unchecked by normal cellular mechanisms, this KRAS protein can result in the disruptive growth of cells we know as tumors. (3) Given this information, the goal of many physicians and researchers is to discover helpful molecules or drugs that specifically target this mutant KRAS protein, and similar targets, to weaken the cancer cells and force their cell death.

How can we stop cancer?

The ultimate goal is to target the crux of the cancer, like the mutant KRAS protein in pancreatic cancer, in a way that does not harm healthy cells. Consider the image above and imagine the cancer cell as a 6-legged table. If you kick out one leg from the table, it will probably not fall over. But, if you kick out half or more of those legs, it will at the least begin to wobble and it may even completely topple. The goal of healthcare, clinical research, and basic science are to understand how to destroy enough legs of the table to make it topple over completely, with no hope of being resurrected. This can be very challenging. Not all cancer types harbor the same mutations, or behave the same way, so specialized treatments need to be developed for each one. In practice, we can do this by understanding the molecular biology of the individual cancer cell types and implementing rationally designed therapies including small molecules, drugs, antibodies, and chemotherapies.

What can we do?

We can all help destroy the table. We can donate our money to fund basic research, volunteer at events that raise awareness for these diseases. We can ask specific questions of our physicians that help us get the most information out of a diagnosis, and share their answers with the public. Knowledge is empowering. By educating ourselves, and understanding how our lifestyles and options for treatments can affect cancer, we will empower ourselves, our families, and our communities to live happy, healthy, and cancer free.

References:

1. The American Cancer Society, www.cancer.org

2. Hanahan, D,, Weinberg, RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70

3. Choi M, Bien H, Mofunanya A, Powers S. Challenges in Ras therapeutics in pancreatic cancer. Semin Cancer Biol. 2017 Nov 20. (17)30235-3

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