Naked and Exposed: Cancer Under the Microscope (Kylie Ainslie)

What is Cancer?: Getting to know the enemy

Cancer is a mysterious illness that seemingly comes in the dead of night, spreads fearlessly, and kills efficiently. For most, cancer is a poorly understood, deadly disease for which a cure remains elusive. In the last few decades researchers’ understanding of cancer has grown exponentially. Cancer is a family of diseases that begin with a small group of cells that grow and divide uncontrollably, and then invade the body via a complex, multistep process. At the root of cancer development are mutations, changes in the genetic code (DNA) resulting from errors in DNA replication, of a subgroup of cells. These mutations alter the normal functions of the cell allowing for better survival. Eventually, those cells best fit for survival acquire more mutations enabling them to survive even better.

Hanahan and Weinberg identify six capabilities enabling tumor[i] formation and spread of cancer cells throughout the body. The six capabilities, or hallmarks, are:

1.     Uncontrolled cell growth and division

2.     Inactivation of tumor suppressing mechanisms

3.     Evasion of programmed cell death

4.     Unlimited replication

5.     Formation of new blood vessels

6.     Ability to invade surrounding tissues and spread throughout the body (metastasis).

Once a cell acquires all six hallmarks, it is classified as cancerous. Hallmarks are not necessarily acquired in the order listed above.

           

http://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer

            The first, and arguably most fundamental, hallmark of cancer cells is uncontrolled cell proliferation (growth and division). Normal cells contain controls that prevent rampant cell division, but cancer cells have developed mutations that disrupt those cellular controls. Similarly, normal cells also possess other mechanisms that suppress the acquisition of hallmarks. The inactivation of these tumor-suppressing mechanisms, enabling mutations to occur, is the second hallmark.

            When cells become old or sustain irreversible stress, such as extensive DNA damage, cell death is initiated. DNA damage can increase the rate of mutation when cell division occurs, so the initiation of cell death removes the threat of future mutations. Cancer cells develop methods to circumvent cell death, which allows the cells to continually divide and increase the chance of acquiring other hallmarks.

            Normal cells can only replicate their DNA a fixed number of times. However, cancer cells must be able to replicate an unlimited number of times to develop large tumors.

            Cancer cells grow and divide at abnormally high rates. To maintain such high activity requires nutrients from blood vessels. To meet excessive energy needs, cancer cells create new blood vessels (angiogenesis). New blood vessels are normally only created during early development and wound healing, but cancer cells can turn the signals to create new vessels back on.

            The sixth hallmark is the ability of cancer cells to invade surrounding tissues and metastasize, spread throughout the body. This hallmark makes cancer so deadly. Cells in the primary tumor break free, enter nearby blood vessels, travel through the vessels, exit the vessels farther downstream, implant in distant tissues, and finally acquire mutations that allow for the formation of secondary tumors in distant tissues. Not all cells that travel from the primary tumor form secondary tumors. Though most cancer cells are eliminated during the journey, those with the most advantageous mutations will form secondary tumors.

(Hanahan and Weinberg 2011)


What now?

            The multitude of research exploding worldwide into cancer mechanisms, characteristics, and therapeutics has increased the ability to detect, treat, and to some extent prevent cancer. For the average person, however, cancer is still shrouded in mystery. Cancer is very complex, but it is important for the general population to understand the basics of cancer causes, progression, and prevention. There has been significant progress in the development of new cancer therapeutics that target hallmark mechanisms (bench to bedside translation). Despite this progress, there is a disconnect between the labs teeming with researchers and the information available to the general population. How can individuals access information about cancer? Doctors are too busy, the internet is a sea of legitimate and bogus information, computers are intimidating to older generations who are at risk for cancer now. Cancer can run amuck in humans long before symptoms appear. Often, cancer is diagnosed long past the stage where any of the myriad of drugs available can be beneficial. The first step in the war on cancer is education, getting to know the enemy.

topics.time.com

Information is power!

            “Cancer is a disease of aging. If you live long enough you will get cancer” (Dr. Doetsch, pers. comm.). Cancer may be inevitable, but the goal is to keep it at bay long enough to live a long, healthy life. Screening for cancer is an excellent way to detect cancer early. Some screening techniques are most effective under certain conditions. For example, mammography, used to screen for breast cancer, is most effective in women over 50 (Mukherjee, 2010). However, patients with a family history of the disease have an increased risk, and should be screened earlier. Women with a family history of breast cancer should be screened as early as in their 30s. Ethnicity also plays a role in cancer risk. African American women have a higher incidence of cancer than their white counterparts. It's important that women understand when they should be screened. Efforts to increase dissemination of information by putting legitimate information on the internet, mailing information to women at risk, offering informational seminars on screening and risks, and opening information hotlines, a number women can call to talk to a medical professional to have their questions answered, should be initiated.

            Screening, however is not free, and often requires patients to go to special clinics. Individuals who live far from clinics or who cannot afford screening are much less likely to be screened. "The United States is the only developed country without a national healthcare system" (Dr. L. Wilke, pers. comm.). In a perfect world, Congress would stop bickering and pass a national healthcare plan that provides low cost or free screening to at risk women. In the mean time, mobile screening centers offering screening for little or no cost should be dispersed in areas without nearby clinics.

            While screening has many benefits, it also poses an ethical dilemma. Why not screen everyone? As technology improves, screening can be performed earlier. "Screening earlier doubles the risk of false positives" (Dr. L. Wilke, pers. comm.). If screening technology is employed too early there is increased risk of false detection, where a person without cancer is diagnosed with cancer. False diagnosis can lead to emotional stress and costly, often invasive, additional tests and treatments. The harm of false diagnosis cements the necessity of programs designed to educate people on appropriate screening.

The implementation of campaigns to educate the population on screening together with initiatives to provide better access to screening can greatly reduce the incidence of cancer related deaths.

References:
Hanahan, D. and R. Weinberg. 2011. Hallmarks of Cancer: The Next Generation. Cell 144:646-674.

Mukherjee, S. 2010. The emperor of all maladies: A biography of cancer. New York, NY: Scribner.

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[i] In this article, “tumor” refers to malignant tumor. Benign tumors are not considered cancerous because they do not invade surrounding tissues and spread throughout the body (i.e. they do not possess all six hallmarks). 

Kylie Ainslie is a first year PhD student in the department of Biostatistics and Bioinformatics at Emory University. She hopes to apply biostatistical methods to cancer research. When not involved in scholastic endeavors, Kylie enjoys running long distances in weather most normal people would elect to stay inside during and coaching softball to a gaggle of mismatched houligans.