Investigatory Project

Cancer:
Prevention & Cure
 Introduction
Cancer is a disease in which some cells grow uncontrollably and spread to other parts
of the body. Cancer can start almost anywhere in the human body, consisting of
trillions of cells.

Mutation
Normally, human cells grow and multiply
through a process called cell division, to
form new cells as the body needs them.
When the cells grow old or become
damaged, they die and new cells take their
place.

Mutations can happen by chance when a

cell is dividing. Some mutations mean that
the cell no longer understands its instructions causing it to grow out of control. There
must be about 6 different mutations before a normal cell turns into a cancer cell. These
cells may form tumors, which are lumps of tissue that can be cancerous or non-
cancerous.

Cancerous tumors spread into, or invade, nearby tissue and can travel to distant places
in the body to form new tumors (a process called metastasis). Cancer tumors may also
be a malignant tumor. Many cancers form solid tumors, but cancers of the blood such
as leukemias, generally do not.
 Metastatic Transformation
of Cancer Cells
Metastasis is a multi-step process encompassing the
� local infiltration of tumor cells into the adjacent tissue,
� transendothelial migration of cancer cells into vessels known as intravasation,
� survival in the circulatory system,
� extravasation and
� subsequent proliferation in competent organs leading to colonization.

Metastasis is known as a very inefficient process

because a coordinated choreography of the
multiple events is required to prevent failure of
the complex process that otherwise runs into the
elimination of emigrating cancer cells at any of
the many steps on the way. Although the
dissemination from a primary tumor of 1 cm size
(roughly corresponding to 1×109 cancer cell) can
infiltrate the circulatory system with one million
cancer cells per day, subsequent colonization is
very limited due to incompatible distal sites. Consequently, < 0.1% of disseminated
cancer cells successfully develop distal metastasis. Albeit, dormant solitary tumor
cells or micrometastases, which represent undetectable cancer cell populations due to
a cell cycle arrest or a balance between proliferation and apoptosis, might eventually
outgrow clinically detectable macrometastases many years post anti-cancer treatment.

Dissemination of cancer cells precedes the initial steps of the invasion-metastasis

cascade. The cascade is the consequence of chromosomal instability that is caused by
continuous errors in chromosome segregation during mitosis. Faults in chromosome
segregation cause the rupture of micronuclei and the secretion of genomic DNA into
the cytosol, which subsequently activates cytosolic DNA-sensing pathways (cyclic
GMP-AMP synthase-stimulator of interferon (IFN) genes) and downstream nuclear
factor K-light-chain-enhancer of activated B signaling.

Studies suggest that the nature of primary seeding cancer cells determines the different
metastatic properties concerning growth and response to therapy. In vivo and in vitro
studies show that metastatic cancer cells migrate individually. In humans, however, it
is believed that seeding requires the joint action of a cluster of tumor cells moving
together, which brings epithelial-mesenchymal transition (EMT) into the picture.

Epithelial-mesenchymal transition
EMT is the transdifferentiation process through which transformed epithelial cells
develop the ability to invade, resist stress, and disseminate. Epithelial cells are
immotile and tightly bound to each other and the neighboring extracellular matrix
(ECM).

EMT governs reversible biochemical alterations that permit a specific epithelial cell to
attain a mesenchymal phenotype and confers epithelial-mesenchymal plasticity upon
epithelial cells, which is crucial for cancer progression and metastasis. However, not
all cells that originate from the primary tumor site contribute to the development of
metastasis. Studying the determinants of metastatic potential in a mouse model of
breast cancer revealed that asparagine synthetase, a metabolic enzyme, is correlated
with metastasis development.

Can metastasis be driven by epigenetic factors?

Age-related physical changes in the ECM promote or inhibit tumor cell motility,
invasion, and metastasis. Alterations in the motility of immune cells lead to changes in
the immune microenvironment. Elderly patients with melanoma tend to develop fewer
metastases in proximal lymph nodes but have more distal metastases, with worse
survival than that of younger cohorts.

Chromatic mutations have recently come to light as important mediators of cancer

development. Chromatic alterations induce cells to gain full oncogenic characteristics.
Furthermore, genetic, environmental, and metabolic conditions influence chromatin to
become permissive or restrictive. Epigenetic plasticity is exhibited when permissive
chromatin induces oncogenic expression to promote metastatic development.
 Causes & Symptoms
Causes
Cancer is a genetic disease—that is, it is caused by changes to genes that control the
way our cells function, especially how they grow and divide. Genetic changes that
cause cancer can happen because:
� Of errors that occur as cells divide
� Of DNA damage caused by harmful substances in the environment, such as the
chemicals in tobacco smoke and ultraviolet rays from the sun.
� They were inherited from their parents.
The body normally eliminates cells with damaged DNA before they turn cancerous.
But the body’s ability to do so goes down as we age. This is part of the reason why
there is a higher risk of cancer later in life.
The genetic changes that contribute to cancer tend to affect three main types of genes
—proto-oncogenes, tumor suppressor genes, and DNA repair genes. These changes
are sometimes called “drivers” of cancer.

Proto-oncogenes are involved in normal cell

growth and division. However, when these
genes are altered in certain ways or are more
active than normal, they may become cancer-
causing genes (or oncogenes), allowing cells
to grow and survive when they should not.

Tumor suppressor genes are also involved in

controlling cell growth and division. Cells with certain alterations in tumor suppressor
genes may divide in an uncontrolled manner.

DNA repair genes are involved in fixing damaged DNA. Cells with mutations in these
genes tend to develop additional mutations in other genes and changes in their
chromosomes, such as duplications and deletions of
chromosome parts. Together, these mutations may
cause the cells to become cancerous.
Environmental factors: Exposures to certain human-made and naturally occurring
chemicals in the environment may contribute to an individual’s risk of developing
cancer. Benzene, asbestos, vinyl chloride. Radon, arsenic, and trichloroethylene are
examples of toxic substances that can increase the risk of cancer when people are
exposed to them.

Symptoms
Cancer can grow into or begin to push on nearby organs, blood vessels, and nerves.
This pressure can cause some of the signs and symptoms of cancer. Common
symptoms include:
� Very heavy night sweats or fever
� Fatigue
� Unexpected bleeding or bruising
� Unusual weight loss
� Unusual lump or swelling anywhere
 Types of Cancer
Cancers may be classified by their primary site or origin or by their histological or
tissue types. By the primary site of origin, cancers may be of specific types like
� breast cancer,
� lung cancer,
� prostate cancer,
� liver cancer
Third most common cancer with a 3-5% survival rate
Major risks: prior infections with hepatitis B and C viruses
Alcohol-induced liver injury ⇒ hepatocellular carcinoma (HCC)
� renal cell carcinoma (kidney cancer),
� oral cancer,
� brain cancer, etc.

Based on tissue types cancers may be classified into six major categories:

Carcinoma
This type of cancer originates from the
epithelial layer of cells that form the lining of
external parts of the body or the internal linings
or organs within the body.

Carcinomas, malignancies of epithelial tissue,

account for 80 to 90 percent of all cancer cases
since epithelial tissues are most abundantly found in the body being present in the skin
to the covering and lining of organs and internal passageways, such as the
gastrointestinal tract. Carcinomas usually affect organs or glands capable of secretion
including breast, lungs, bladder, colon, and prostate.

Carcinomas are of two types - adenocarcinoma and squamous cell carcinoma.

Adenocarcinoma develops in an organ or gland which may affect mucus membranes
and is first seen as a thickened plaque-like white mucosa. Squamous cell carcinoma
originates in squamous epithelium. These are rapidly spreading cancers.
Sarcoma
These cancers originate in the connective and supporting tissue including muscles,
bones, cartilage, and fat. Bone cancer is one of the sarcomas termed osteosarcoma. It
affects the young most commonly. Sarcome appear like the tissue in which they grow.

Some more examples include chondrosarcoma (of the cartilage), fibrosarcoma

(fibrous tissue), Hemangioendothelioma (blood vessels), liposarcoma (adipose or fatty
tissue), etc.

Myeloma
These originate in the plasma cells of the bone arrow. Plasma
cells are capable of producing various antibodies in response
to infections. Myeloma is a type of blood cancer.

Leukemia
This is a group of cancers that are grouped within blood
cancers. These cancers affect the bone marrow which is the
site for blood cell production. When cancerous, the bone
marrow begins to produce excessive immature white blood
cells that fail to perform their usual actions and the patient is
often prone to infection.

Types of leukemia include

� Acute myelocytic leukemia (AML) - these are
malignancies of the myeloid and granulocytic
white blood cell series seen in childhood.
� Chronic myelocytic leukemia (CML) - this is seen in adulthood.
� Acute Lymphatic, lymphocytic, or lymphoblastic leukemia (ALL) –
these are malignancies of the lymphoid and lymphocytic blood cell
series seen in childhood and young adults.
� Chronic Lymphatic, lymphocytic, or lymphoblastic leukemia (CLL) –
this is seen in the elderly.
� Polycythemia vera or erythremia – this is cancer of various blood cell
products with a predominance of red blood cells.
Lymphoma
These are cancers of the lymphatic system. Unlike leukemias, which affect the blood
and are called “liquid cancers ', lymphomas are “solid cancers”. These may affect
lymph nodes at specific sites like the stomach, brain, intestines, etc. These lymphomas
are referred to as extranodal lymphomas.

Lymphomas may be of two types - Hodgkin’s lymphoma and non-Hodgkin’s

lymphomas. In Hodgkin lymphoma, there is a characteristic presence of Reed-
Sternberg cells on the tissue samples which are not present in Non-Hodgkin
lymphoma.

Mixed Types
These have two or more components of cancer. Some examples include mixed
mesodermal tumors, carcinosarcoma, adenosquamous carcinoma, and
teratocarcinoma. Blastomas are another type that involves embryonic tissues.
 Diagnosis
The diagnosis of cancer entails an attempt to identify accurately the anatomical site of
origin of the malignancy and the type of cells involved. Cancer can arise in any organ
or tissue in the body (such as the lung, breast, cervix, colon, and rectum). The term
site refers to the location of the cancer within the body. The term histology refers to
the type of cells involved.

Identifying the site is important because tumors in different organs or tissues of the
body behave differently. Identifying cell types is important because various
histological types have different growth rates and dissimilar prognoses. More than one
histological type of cell may be found in the same site. For example, a tumor whose
primary site is skin can be basal cell carcinoma, squamous cell carcinoma, or
melanoma.

The histological type is determined by microscopic examination of suspected tissue

which has been excised by biopsy or surgical resection. If the histological type is not
that usually found in the tissue being examined, it means the cancer has spread to that
area from the primary site by direct extension, by metastasis via the bloodstream or
the lymphatic system, or by seeding or implantation of cancer cells.

There is no single test that can accurately diagnose cancer. The complete evaluation of
a patient usually requires a thorough history and physical examination along with
diagnostic testing. Many tests are needed to determine whether a person has cancer, or
if another condition (such as an infection) is mimicking the symptoms of cancer.

Effective diagnostic testing is used to confirm or eliminate the presence of disease,

monitor the disease process, and plan for and evaluate the effectiveness of treatment.
In some cases, it is necessary to repeat testing when a person’s condition has changed,
if a sample collected was not of good quality, or if an abnormal test result needs to be
confirmed.
Cancer diagnosis methods:
� Lab tests
� Diagnostic imaging
� Endoscopic exams
� Genetic tests
� Tumor biopsies

Lab Tests
Clinical chemistry uses chemical processes to measure levels of chemical components
in body fluids and tissues. The most common specimens used in clinical chemistry are
blood and urine.
Many different texts exist to detect and measure almost any type of chemical
component in blood or urine. Components may include blood glucose, electrolytes,
enzymes, hormones, lipids (fats), other metabolic substances, and proteins.

The following are some of the more common laboratory tests:

� Blood tests
� Complete blood count (CBC)
� Urinalysis
� Tumor markers

Diagnostic imaging
Diagnostic radiology has greatly
advanced in recent years with the
development of new instruments and
techniques that can better detect cancer
and also help patients avoid surgery.

Imaging is the process of producing

valuable pictures of body structures and
organs. It is used to detect tumors and
other abnormalities, to determine the extent of disease, and to evaluate the
effectiveness of treatment. Imaging may also be used when performing biopsies and
other surgical procedures. There are three types of imaging used for diagnosing
cancer: transmission imaging, reflection, and emission imaging. Each uses a different
process.
Transmission imaging
X-rays, computed tomography scans (CT scans), and fluoroscopy are radiological
examinations whose images are produced by transmission. In transmission imaging, a
beam of high-energy photons is produced and passed through the body structure being
examined. The beam passes very quickly through less dense types of tissue such as
watery secretions, blood, and fat, leaving a darkened area on the X-ray film. Muscle
and connective tissues (ligaments, tendons, and cartilage) appear gray. Bones will
appear white.

� X-ray
� Computed tomography scan (also called a CT scan or computed axial
tomography or CAT scan)
� Bone scan
� Lymphangiogram (LAG)
� Mammogram

Reflection imaging
Reflection imaging refers to the type of imaging produced by sending high-frequency
sounds to the body part or organ being studied. These sound waves “bounce” off of
the various types of body tissues and structures at varying speeds, depending on the
density of the tissues present. The bounced sound waves are sent to a computer that
analyzes the sound waves and produces a visual image of the body part of the
structure.

Emission imaging
Emission imaging occurs when tiny
nuclear particles or magnetic energy are
detected by a scanner and analyzed by
computer to produce an image of the
body structure or organ being examined.
Nuclear medicine uses emission of
nuclear particles from nuclear substances
introduced into the body specifically for
the examination. Magnetic resonance
imaging (MRI) uses radio waves with a
machine that creates a strong magnetic
field that in turn causes cells to emit their
own radio frequencies.
An MRI does not use ionizing radiation (X-rays) and is a non-invasive medical test or
examination. The MRI machine uses a large magnet and a computer to take pictures
of the inside of your body. Each picture or “slice” shows only a few layers of body
tissue at a time. The pictures can then be examined on a computer monitor.

Pictures taken this way may help caregivers find and see problems in your body more
easily. The scan usually takes between 15 to 90 minutes.
Including the scan, the total examination time usually takes between 1.5 to 3 hours.

A substance called gadolinium is injected into a vein to help the physicians see the
image more clearly. The gadolinium collects around cancer cells and they show up
brighter in the picture. Sometimes a procedure called magnetic resonance
spectroscopy (MRS) is done during the MRI scan. An MRS is used to diagnose
tumors based on their chemical make-up.

Endoscopic examinations
Types of endoscopies include:
� Cystoscopy (also called cystourethroscopy)
� Colonoscopy
� Endoscopic retrograde cholangiopancreatography (ERCP)
� Esophagogastroduodenoscopy (also called EGD or upper endoscopy)
� Sigmoidoscopy

Genetic testing
Testing for mutations in genes that give an increased risk for cancer is complicated.
The concepts are important to understand when considering cancer susceptibility gene
testing.

Tumor Biopsies
A biopsy is a procedure performed to remove tissue or cells from the body for
examination under a microscope. Some biopsies can be performed in a physician’s
office, while others need to be done in a hospital setting. In addition, some biopsies
require use of an anesthetic to numb the area, while others do not require any sedation.

Biopsies are usually performed to determine whether a tumor is malignant (cancerous)

or to determine the cause of an unexplained infection or inflammation.
The following are the most common types of biopsies:
� Endoscopic biopsy
� Bone marrow biopsy
� Excisional or incisional biopsy
� Fine needle aspiration biopsy
� Punch biopsy
� Shave biopsy
� Skin biopsy

Cancer staging
Staging is a way of describing the size of a cancer and how far it has grown. When
doctors first diagnose cancer they carry out tests to check:
� how big the cancer is
� whether it has spread into surrounding tissues or other parts of the
body.

The TNM staging

T describes the size of the tumor and how far it has spread into the nearby tissue. It
can be 1, 2, 3 or 4, with 1 being small and 4 large.
N describes whether the cancer has spread to the lymph nodes. It can be between 0
and 3. 0 means that there are no lymph nodes containing cancer cells and 3 means that
there are lots of lymph nodes containing cancer cells.
M describes whether the cancer has spread to a different body part. It can either be 0
or 1. M0 means that cancer hasn’t spread and M1 means that the cancer has spread.

The number system

Most types of cancer have 4 stages.
Stage I: the cancer is small and contained within the
organ.
Stage II: the cancer is larger than stage I but hasn’t
spread to surrounding tissues. Sometimes stage II means
that cancer cells have spread into lymph nodes close to
the tumor.
Stage III: the cancer may have spread to surrounding
tissues and lymph nodes.
Stage IV: the cancer may have spread to another body organ. It is also called
metastatic cancer or secondary cancer.
 Treatment
Cancer is treated in several ways, depending on each person’s medical condition and
type of cancer. Common treatments involve chemotherapy and radiation therapy.
Other treatments include surgery and biological therapies.

For many people with cancer, treatment is a process that is designed to meet their
needs. Doctors plan treatments based on several key factors, such as the type and stage
of the cancer, as well as the person’s age, health and lifestyle.

Cancer treatment terms:

Combined modality therapy
A term used to describe when doctors choose more than one therapy in treating a
patient, such as a combination of radiation therapy and chemotherapy.

Adjuvant therapy
A term used to describe when doctors choose more than one therapy in treating a
patient. However, the term adjuvant therapy is more specifically used to describe
treatment given after the primary cancer treatment is completed to improve the chance
of a cure. For example, if the doctor wants to treat cancer cells that may be prescribed
one or more additional treatments.

Neoadjuvant therapy
A term used to describe when doctors choose to use more than one therapy in treating
a patient. However, the term neoadjuvant therapy is more specifically used to describe
cancer treatment given before the primary therapy -- noth to kill any cancer cells and
to contribute to the effectiveness of the primary therapy.
Cancer treatment methods
Cancer is treated in several ways, depending on each person’s medical condition and
type of cancer. Common treatments involve chemotherapy and radiation therapy.
Other treatments include surgery and biological therapies.

For many people with cancer, treatment is a process that is designed to meet their
needs. Doctors plan treatments based on several key factors, such as the type and stage
of the cancer, as well as the person’s age, health, and lifestyle. If you have been
diagnosed with cancer, it is important for you to know that you play an important role
in the treatment process. Offering input, asking questions, and expressing your
concerns about treatment can help make treatments a better experience.

How is Surgery used in Cancer Treatment?

Surgery is used in several ways to help cancer patients. According to the American
Cancer Society (ACS), it is the oldest form of cancer treatment. It provides the best
chance to stop many types of cancer, and it also plays a part in diagnosing, staging,
and supporting cancer treatment.

Undergoing surgery for cancer is different for every patient, depending on the type of
surgery, the type of cancer, and the patient’s health. For some people, surgery is a
major medical procedure with life-changing side effects. For others, surgery is quick
and has few side effects.

Radiation Therapy
Radiation therapy is a form of high energy x-ray which can destroy or prevent the
spread of cancer. The goal is to target cancer, while minimizing exposure to
surrounding healthy cells. Treatment varies by the location of the cancer.

Chemotherapy
This group of medications stops the growth of rapidly
dividing cells in the body, both cancerous and
noncancerous. While powerful, chemotherapy can
cause more side effects than other medication types.
Chemotherapy is a treatment option for many
cancers, but there are cancers that respond better to
other types of medication, surgery, or radiation
therapy.
Hormone Therapy
Tumors that appear in the breast, prostate, endometrium (the inner lining of the
uterus), and ovaries are often hormone sensitive. Hormone therapy can reduce in size
or even eliminate these cancers by manipulating the hormones that fuel them.

Hormone therapy is often used following surgery, radiation therapy, or chemotherapy,

but in many cases it can be its own stand-alone treatment.

Biological Therapy
Biological therapy is treatment with substances that are made naturally in the body or
that can block the growth of cancer cells. This approach is designed to minimize the
side effects associated with traditional treatments like chemotherapy.

Biologic therapies are produced in a laboratory and given to patients to:

� Boost the body’s ability to fight the disease
� Direct the immune system’s disease fighting powers to disease cells
� Strengthen a weakened immune system

Types of biological therapy

Biologics include nonspecific immunomodulating agents, interferons, interleukins,
colony-stimulating factors, monoclonal antibodies and vaccines.
� Trastuzumab is the most common biological therapy used for breast cancer. It
is a type of monoclonal antibody that attaches to the Her2 receptor, a particular
type of protein on some breast cancer cells that make them grow. Herceptin
blocks the signals and can slow or stop the growth of the tumor, as well as also
increase the effect of chemotherapy drugs on breast cancer cells.
� Lapatinib against HER2-positive breast cancers by blocking certain proteins
that can cause uncontrolled cell growth.
� Bevacizumab is an angiogenesis inhibitor that works by blocking the growth of
new blood vessels that cancer cells depend on to grow and function.

Blood and Marrow Transplants

Blood and marrow transplant (BMT) is a procedure to replace blood-forming cells
(stem cells) that are damaged by certain diseases. Autologous transplant uses stem
cells that are collected from you to repopulate your bone marrow after high dose
chemotherapy. Allogeneic transplant uses stem cells collected from a donor.
Infusion of the stem cells is done after the preparative therapy, which is chemotherapy
with or without radiation therapy. The chemotherapy can kill cancer cells, but may
also kill the blood cells in the bone marrow. The subsequent infusion of the stem cells
replaces the blood cells destroyed by the cancer treatment.

A BMT is a treatment for people who have been diagnosed with lymphoma, leukemia,
or multiple myelomas, and other non-cancerous disorders of the blood.

Immunotherapy
These medications slow the growth and spread of cancer by provoking the body’s
immune system to fight disease. Immunotherapy treatments are the newest class of
anticancer drugs. Some available for treatment today; others are being developed and
will be available for treatment soon.

Angiogenesis Inhibitors
Angiogenesis, the formation of new blood vessels, is a process controlled by certain
chemicals produced in the body. Although this may help in normal wound healing,
cancer can grow when these new blood vessels are created. Angiogenesis provides
cancer cells with oxygen and nutrients. This allows the cancer cells to multiply,
invade nearby tissue, and spread to other areas of the body (metastatize).

Conditions treated:
� Colorectal cancer
� Cutaneous T-cell lymphomas (CTCL)
� Lung cancer
� Mycosis fungoides
� Prostate cancer
� Sezary syndrome
 Preventive Measures
Between 30-50% of all cancer cases are preventable. Prevention offers the most cost-
effective long-term strategy for the control of cancer.

Tobacco
Tobacco smoke has more than 7000 chemicals, at least
250 are known to be harmful and at least 69 are known
to cause cancer. Tobacco use (including cigarettes,
cigars, hookah, chewing tobacco and more) has been
linked to many types of cancer, including lung,
colorectal, breast, throat, cervical, cladder, mouth and
esophageal cancers. It’s best never to start using
tobacco, but if you do use tobacco products, it’s never
too late to quit.
Smoking still accounts for about 30% of all cancer deaths. About 80-90% of all lung
cancers are related to smoking.

Alcohol
Alcohol use increases the risk for many cancer types including cancer of the oral
cavity, pharynx, larynx, esophagus, liver, colorectal and breast. To reduce your risk of
cancer, it’s best to avoid alcohol completely. The more you drink, the greater your risk
of cancer. Even small amounts of alcohol
might increase your risk.

Plant-based diet
Eat lots of fruits, vegetables, beans and
whole grains, limit red meat and food high
in salt and cut out processed meats. Avoid
drinks with added sugar. A large 2021 study
found that three servings of vegetables (not
starchy ones, like potatoes) and two of fruit
everyday resulted in a 10% lower risk of
death from cancer.
Maintain a healthy weight and be physically active
Obesity is linked to many cancers, including those of the endometrium, liver, kidney,
pancreas, colon, breast (especially in post-menopausal women) and more.

Getting at least 30 minutes of physical activity at least 5 days a week can make a big
difference in your general health and well-being. Make it a priority to move more and
sit less. If you spend most of your time at work sitting at a desk, for example, find a
way to get up and move around every hour.

Physical activity is linked to a lower risk of colorectal, breast and endometrial cancers,
and there is some evidence that also links it to reducing the risk of other cancers. Add
exercise to your routine to reduce stress, increase energy, boost your immune system,
control your weight and reduce your risk of cancer.

Protection from the sun

High sun exposure directly increases the risk of melanoma (skin
cancer). Tanning beds and indoor tanning are carcinogenic to
humans as it can increase the risk of melanoma by around 20
percent.

To lower the risk of skin cancer, one must avoid the sun during
peak burning hours, wear long sleeve shirts, long pants, and wide-
brimmed hats, properly apply and reapply broad-spectrum
sunscreen.
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Books
Methods of cancer diagnosis, therapy and prognosis page: xvii
Cancer characteristic and selection of cases: book 2: pg 34