Hargett 1

Aidan Hargett

Stanard

ENG 1201

18 July 2021

An “Evolution” in Cancer Prevention and Treatment

By 2020, over 15 million people (about twice the population of New Jersey) are expected

to wake up one day with cancer, and 10 million are expected to take their final breath because of

the disease (“Cancer Burden Will Increase as Population Grows, Ages” 2). Each day families,

rocked with the dreadful news of tumors and cancers, dream of a world without chemotherapy

and radiotherapy. A novel approach, a genetic one, might soon fulfill that dream. It is commonly

known that detecting cancer early is the best defense any affected person may have. The newly

emerging field of research in genomics uses preventative techniques based on the detection of

the formation and evolution of cancer to quickly isolate and specialize the treatment. The use of

genomics in the prevention, identification, and treatment of cancer, although it requires more

research, is a promising and encouraging alternative to traditional methods of treatment and

research.

Before one may understand the importance of genetics in the treatment and detection of

cancer, one must understand what cancer is and what causes it. As Ondrej Podlaha, an author for

the US National Library of Medicine, writes, “Human tumors result from an evolutionary

process operating on somatic cells within tissues, whereby natural selection operates on the

phenotypic variability generated by the accumulation of genetic, genomic and epigenetic

alterations” (2). In Figure 1 (below), these various levels of alteration are depicted and described
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based on the levels they occur in the cell. Sometimes, not always, these alterations can affect

natural processes that the body normally carries out, including the growth, reproduction, and

death of cells. Alterations and abnormalities that occur at larger levels will have a greater impact

on the functionality of the cell and these processes. Cancer cells often exhibit an abnormality in

at least one of these natural processes, if not all. As a result of this, cancer is described as an

abnormal and uncontrolled division of cells in specific parts of the body. The study and treatment

of cancer are classified under the field of oncology.

Figure 1 Genetic and epigenetic determinants of cancer genome evolution. The highest

level comprises chromosome packaging into the cell nucleus (a). DNA strands in close spatial

proximity are more likely to interact during replication and transcription, leading to

chromosomal rearrangements and gene fusions (b). Aberrant methylation and acetylation of
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histone tails can result in gene expression and splicing variation (c). DNA sequence alterations

may modulate gene expression and change protein amino acid composition (d). Aberrations at all

of these levels may influence the mutational landscape of cancer genomes and the development

of a tumor (Podlaha).

Cancers are classified into two main groups, somatic cancer, and inherited, or germline

cancer. Inherited cancers are cancers that are caused by genetic mutations contained within

gametes, often called sex cells or reproductive cells. These reproductive cells are what fuse to

form offspring, meaning, both men and women, often in conjunction with the other, may spread

the disease to offspring. Inherited cancers can often be combatted by artificial selection during

the production of offspring. Preventative measures for germline cancers already exist and are

used quite effectively. Due to this, somatic cancer is the most generic form of any cancer in the

world and is the hardest cancer to detect and treat without proper preventative measures. Somatic

cancers refer to cancers developed within any region of the body, besides the reproductive cells.

“Somatic genomic alterations are DNA sequence aberrations that have accumulated in the

genome of a cell during the lifespan of the patient” (Podlaha 4). Due to the large nature of the

body, somatic cancers are more common and increasingly more deadly.

The use of genomics to treat and identify cancer is something that has only recently been

viewed as a possibility. Genomics is the study of the genes in the body, known as the genome,

and how it affects the physical expression of cells. Bruce Silver goes on to write about how

"modern genomic and molecular technologies have enabled advances in our understanding of

pathogenetic pathways in oncogenesis” (1). The use of genomics to classify and distinguish

between different natural cancers that appear identical is a recent thing, but more recent

treatments and studies have occurred to better understand and treat cancers.
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The importance of genetics in the understanding of cancer is obvious, a mutation or

change in the genome of a patient causes tumors, understanding why, how, and when these

changes occur allows for scientists and oncologists to better understand and treat specific

cancers. Before the use of genomics and genome sequencing, cancers were understood and

classified based on a system of histopathologic appearance. This means, under a microscope,

scientists observed cancer cells and classified them solely on appearance. “This molecular

heterogeneity results in genetic subtyping of histologically identical tumors into groups with

significantly different natural histories and responses to therapeutic agents” (Silver 1). Previous

treatments based on these identification methods proved to be ineffective, as the treatments used

were often paired up with the incorrect and wrong types of cancer.

Silver goes on to explain that as oncologists “acquire the technologies to delineate

genomic subgroups within particular tumor histologies” (3), the use of old, costly, and unreliable

clinical development to denote types of cancers will slowly end. For example, in a study

summarized by Atsushi Tanaka, scientists used genomics and protein sequencing to detect and

treat colorectal cancer. She states that genomicists “used unbiased deep proteomics to identify

proteome signatures that quantitatively differentiate colorectal cancer from benign colonic

mucosa (a histopathologically similar disease)” (17). The expression and identification of

specific proteins allow scientists to apply and differentiate between similar types of cancer, all of

which was done through the use and understanding of genomics.

On top of this, the same protein used to identify colon cancer, DDX21, also serves as a

treatment for colon cancer itself. Tanaka writes, when “564 early-stage cases were analyzed

together, patients with positive DDX21 protein expression had both significantly longer overall

survival and disease-free survival times than patients with negative DDX21 protein expression”
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(16). Oncologists identified that the expression of this protein, only correlated through methods

in genomics, resulted in higher survival rates in patients with colorectal cancer. Figure 2, below,

depicts the location and the sequence that the gene is transcribed to produce the protein DDX21.

This gene was only recently sequenced and identified as the source of DDX21 in December of

2013. This introduces a new treatment for those suffering from colorectal cancer and one that

also produces statistically significant survival rates. The importance of this is self-explanatory,

using genomics, scientists were able to identify and even treat a type of colorectal cancer,

leading to greater survival rates.

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Figure 2 Location and diagram of the exons taken from DNA to produce the protein

DDX21 used in the identification and treatment of colorectal cancer. Transcripts are taken via

genetic sequencing methods of the human genome (Huret).

In another study, oncologists look at a group of family members with concurrent cancer.

Concurrent cancer cases are rarely studied and occur when more than two tumors, or cancers, are

discovered in one or more organs. With the help of genomic sequencing, cheaper methods of

identification to help denote between types of treatments are possible. Oncologists performed a

whole-exome sequence whereby they extract the DNA that encodes for proteins and cellular

function from an affected cell and compare for abnormalities in the affected DNA to that of

DNA from a normal cell. Through this, scientists discovered that just sixteen genes could cause

the disorder. As a result of the breakthrough technologies in genetic sequencing, Yin explains

that “through WES and bioinformatics analysis, probable somatic mutations were identified in

the NDUFS7 gene, and germline mutations were identified in 16 candidate genes” (12). These

findings, only available through breakthrough genetic technology, allowed scientists to

selectively act against and stop the transfer of the affected germline mutations in any following

generations of the family, effectively stopping the spread of the cancer. This treatment was not

previously possible without the types of genetic sequencing available today.

Many screenings are common in modern medicine to prevent certain cancers. An

ordinary procedure done to prevent colon cancer is a colonoscopy, however, this does not truly

benefit those most at risk of succumbing to the disease. As an article posted through the National

Cancer Institute states, “because colonoscopy is invasive and the preparation can be difficult, it’s

possible that only the older participants who were fit and healthy underwent this screening test”

(4). Although preventative measures for colon cancer exist, only certain, specific groups can
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benefit from them. The groups most at risk, those who are less healthy and more susceptible to

the immune system failure that cancers bring, are usually not the ones receiving the preventative

screening. Dr. Chan, later in the same article, explains a viable alternative to the highly specific

requirements for screening using colonoscopies, “I hope we will reach a point where we can start

to think about more sophisticated ways...for example, by looking at certain lifestyle factors or

genetic risk factors that predispose some people to the disease” (4). Proposed as an alternative to

current testing, genetic risk pooling is non-invasive and is exceptionally reliable in determining

those who are predisposed to not only colon cancer but any cancer for that matter.

One of the most promising treatments for any form of cancer involves the use of the

differentiation properties of stem cells. A stem cell, by definition, “is any precursor cell that has

the capacity for both replication and differentiation” (Renehan 1). In other words, stem cells are

the root of any type of cell in the body. Before neurons are made in a person, stem cells must

differentiate and specialize into these predetermined types of cells. Before the skin cells are

produced throughout a person’s dermis, stem cells must differentiate into those cells. Stem cells

are the basis and foundation for all cells in the body. Oncologists are using the regenerative

properties of stem cells to replicate and replace the affected and cancerous cells in the body. One

specific instance of the application of stem cells includes the Bcl-2 gene in the stem cells of the

large intestine in mice. Due to the nature of Bcl-2 as an anti-apoptotic ‘survival’ gene, the cell

will avoid apoptosis at all costs. As Andrew Renehan writes in his correlation between stem cells

and cancer, he describes a scenario where a stem cell in the large intestine may become damaged

and attempt to undergo programmed cell death (apoptosis). He says, “low levels of damage may

be inefficiently detected or misrepaired, thus providing another possible explanation for the

increased cancer risk in the large bowel compared with the small intestine” (6). The Bcl-2 gene
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may accidentally misinterpret the extent of the damage in a cell and instead of killing the cell and

avoiding any possibility of an abnormal rate of growth or division, the Bcl-2 gene will promote

the cell to attempt and repair its DNA. This is where the cell will abnormally divide and cause a

tumor. The understanding of this gene in a stem cell of a completely different animal allows

oncologists to apply this logic to a similar gene in humans, and prevent cancers caused by anti-

apoptotic genes.

Throughout the evolution in identification, treatment, and understanding of cancer, no

breakthroughs have been as important as the implication of genetics into the understanding of

oncogenesis. Simply applying basic concepts in genetics to modern medicine allows for many

breakthroughs and discoveries to treat and prevent some of the deadliest forms of cancer.

Alarmingly, cancer rates are swiftly increasing, and “based on current rates, the 10 million new

cases in 2000 will increase by 25 percent in the next 20 years, and by 2050, the number of new

annual cancer cases will be almost 24 million” (“Cancer Burden Will Increase as Population

Grows, Ages” 9). Not only are the rates of infection rising, but so is the mortality rate as “the

number of cancer deaths are estimated to rise from 6 million in 2000 to 10 million in 2020 and

16 million in 2050” (“Cancer Burden Will Increase as Population Grows, Ages” 10). Through

these rising infection rates, the study and use of genomics to treat cancer are quickly coming to

the aid of the millions affected, beginning with a new way to effectively differentiate and classify

diverse types of cancers. Genomics has helped shape the understanding and treatment of

conventional cancers that have, in the past, been misdiagnosed. Through the understanding of

mutations in somatic cells throughout the body, oncologists can classify and specifically identify

mutations that can cause somatic cancers, and, using proteins, they are also able to swiftly

identify and treat specific types of cancers. The use and real-world implications of genetic
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research in oncology and medicine are just beginning, yet the results are already beacons of hope

for the future.

Works Cited

“Cancer Burden Will Increase as Population Grows, Ages.” Nation’s Health, vol. 31, no. 10,

Nov. 2001, p. 13. EBSCOhost, search.ebscohost.com/login.aspx?

direct=true&db=a9h&AN=5456366&site=ehost-live.

Huret, Jean-Loup. “DDX21 (DExD-Box Helicase 21).” Atlas of Genetics and Cytogenetics in

Oncology and Haematology, 15 Mar. 2019,

atlasgeneticsoncology.org/Genes/GC_DDX21.html.

NCI Staff. “Colorectal Cancer Screening in People Over 75.” National Cancer Institute, 15 June

2021, www.cancer.gov/news-events/cancer-currents-blog/2021/colorectal-cancer-

screening-people-older-than-75.

Podlaha, Ondrej, et al. “Evolution of the Cancer Genome.” Trends in Genetics : TIG, U.S.

National Library of Medicine, 16 Feb. 2012,

www.ncbi.nlm.nih.gov/pmc/articles/PMC3711268/.

Renehan, Andrew G., and Christopher S. Potten. “Stem Cells and Cancer.” Encyclopedic

Reference of Cancer, Jan. 2001, pp. 846–853. EBSCOhost,

search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=23678806&site=ehost-live.

Silver, Bruce A. “Molecular and Genomic Research: Assessing the Impact.” Applied Clinical

Trials, vol. 14, Apr. 2005, pp. 8–11. EBSCOhost, search.ebscohost.com/login.aspx?

direct=true&db=a9h&AN=16696530&site=ehost-live.
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Tanaka, Atsushi, et al. “DEAD-Box RNA Helicase Protein DDX21 as a Prognosis Marker for

Early Stage Colorectal Cancer with Microsatellite Instability.” Scientific Reports, vol. 10,

no. 1, Dec. 2020, pp. 1–13. EBSCOhost, doi:10.1038/s41598-020-79049-9.

Yin, Yifa, et al. “Whole Exome Sequencing Study of a Chinese Concurrent Cancer Family.”

Oncology Letters, vol. 18, no. 3, Sept. 2019, pp. 2619–2627. EBSCOhost,

doi:10.3892/ol.2019.10573.