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TANIYA .M.S
INSIGHT INTO CANCER

Cancer is a generic term for a large group of diseases characterized by the unlimited
growth of abnormal cells beyond their usual boundaries that can then invade adjoining
parts of the body and/or spread to other organs.
CANCER

Cancer is the second leading cause of death globally, and is responsible for an estimated
9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer.

Tobacco
Ionising Radiation
Diet and obesity
Excessive
drinking
alcohol
Infections
Stress
Environmental pollutants
Around 1/3 of deaths from cancer are due to the 5 leading behavioural and dietary risks:
high body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use,
and alcohol use.
Risk Factors

Mutations in key regulatory genes (tumor suppressors and proto-oncogenes) alter the
behavior of cells and can potentially lead to the unregulated growth seen in cancer.
Proto-oncogene
•It is a normal gene that could become an oncogene due to mutations or
increased expression.
•Proto-oncogenes code for proteins that help to regulate the cell growth and
differentiation. Upon acquiring an activating mutation, a proto-oncogene
becomes a tumor-inducing agent, an oncogene.
Tumor suppressor
•Genes represent the opposite side of cell growth control, normally acting to
inhibit cell proliferation and tumor development.
Epigenetic Changes
•Gene expression can be altered by changes to the DNA and chromatin that do
not change the genetic sequence.
•Methylation - Some nucleotides in the DNA are modified by the addition of a
methyl group which is associated with the inactivation of that region of DNA
•Acetylation - Addition of acetyl groups loosens the DNA and increases gene
expression.
Mutations

• Point mutations (e.g., RAS)
• Partial deletion mutations (e.g., RTKs)
•Chromosomal translocations that produce novel fusion proteins (e.g., Bcr-Abl)
• Chromosomal translocation to juxtapose a strong promoter upstream and the
proto- oncogene such that it is inappropriately expressed (e.g., cMyc)
• Gene amplification resulting in overexpression (e.g., N-Myc)
•Exogenous sequences.
• Cervical cancer – HPV (human papilloma viruses)
• Burkitt’s lymphoma – EBV (Epstein-Barr virus)
• Hepatocellular carcinoma – hepatitis viruses
Proto oncogenes to oncogenes

Role of p53 (Tumor suppressor)

•Apoptosis is known to potentialy eliminate malignant cell hence the reduction of
apoptosis can be considered to play a key role in carcinogenesis.
Cells frequently die by a process termed programmed cell death or apoptosis.
Apoptosis is the cellular equivalent of a “self destruct” button.
Apoptosis is a very orderly process during which the genome of the cell is broken
down, the cell is fragmented into smaller pieces and the debris is consumed by
nearby cells (phagocytes) that clean up the cell fragments.
•Commonly there are three mechanisms by which apoptosis acquire resistance or
reduction
1 Disruption in balance of apoptotic and antiapoptotic bodies proteins
2 Reduction in function of caspases
3 Impaired death receptors signaling

Benign and malignant tumours
Benign tumours
•Usually grow quite slowly
•Don't spread to other parts of the body
•Usually have a covering made up of normal cells
•Benign tumours are made up of cells that are quite similar to normal cells.
They will only cause a problem if they:
•Grow very large
•Become uncomfortable or painful
•They are visible and unpleasant to look at
•Press on other body organs
Malignant tumours are made up of cancer cells.
They:
•Usually grow faster than benign tumours
•Spread into surrounding tissues and cause damage
•May spread to other parts of the body in the bloodstream or through the lymph
system to form secondary tumours. This is called metastasis

Types of Cancer
•Carcinomas in epithelial cells, organs such as the lung, skin, breast, liver, and pancreas.
•Sarcomas, in contrast, arise from mesenchymal tissues, occurring in fibroblasts, myocytes,
adipocytes, and osteoblasts.
•Nonepithelial tumors can also develop in cells of the nervous system (e.g., gliomas,
neuroblastomas, and medulloblastomas) and hematopoietic tissues (leukemia).

Briefly,
The meta-static process consists of
1) Invasion of metastatic cancer
Cells into the local tissue at the
primary tumor site.
2) Vascularization of the primary
tumor for their aggressive growth.
3)Intravasation of metastatic cancer
cells into blood or lymph vessels.
4) Survival in the circulation.
5) Extravasation from the circulation
to distant sites.
6) Proliferation in a new environment.
Tumor metastasis

The cancer cells without blood circulation grew to 1–2 mm3 in diameter. but grew
beyond 2 mm3 when placed in an area where angiogenesis was possible. In the absence
of vascular support, tumors may become necrotic or even apoptotic

The most cancer cells use glucose at high level and convert it to lactate instead of
relying on mitochondrial oxidative phosphorylation to generate energy even with
adequate oxygen, a phenomenon termed “Warburg effect.”

How Cancer is Diagnosed?
Imaging Procedures
CT Scan
Nuclear scan
Ultrasound
MRI
PET scan
X-rays
Biopsy
Blood tests used to diagnose cancer include:
Circulating tumor cell tests: Detect cells that have broken away from an original
cancer site and are floating in the bloodstream.
Tumor marker tests: Prostate-specific antigen (PSA) - Prostate cancer,
cancer antigen 125 (CA 125) - Ovarian cancer
Complete blood count (CBC) : Measures the amount of various types of blood cells
in a sample.
DR-70: A simple blood test that screens for 13 different cancers at the same time.
Cancers that can be detected by the test are of the lung, colon, breast, stomach,
liver, rectum, ovary, cervix, esophagus, thyroid, and pancreas, and trophoblast and
malignant lymphoma.

Cancer Staging
The TNM system is the most widely used cancer staging system.
•T - size and extent of the main tumor.
•N- the number of nearby lymph nodes that have cancer.
•M -whether the cancer has metastasized.
for example, T1N0MX or T3N1M0. :
•TX: Main tumor cannot be measured.
•T0: Main tumor cannot be found.
•T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the
number after the T, the larger the tumor or the more it has grown into nearby tissues.
T's may be further divided to provide more detail, such as T3a and T3b.
•NX: Cancer in nearby lymph nodes cannot be measured.
•N0: There is no cancer in nearby lymph nodes.
•N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer.
The higher the number after the N, the more lymph nodes that contain cancer.
•MX: Metastasis cannot be measured.
•M0: Cancer has not spread to other parts of the body.
•M1: Cancer has spread to other parts of the body

Stage What it means
Stage 0
Abnormal cells are present but have not
spread to nearby tissue. Also called
carcinoma in situ, or CIS. CIS is not cancer,
but it may become cancer.
Stage I, Stage II, and Stage III
Cancer is present. The higher the number,
the larger the cancer tumor and the more it
has spread into nearby tissues.
Stage IV
The cancer has spread to distant parts of the
body.
Another method

SURGERY
•Surgery is the removal of the tumor and surrounding tissue during an operation.
•Treating cancer with surgery works best for solid tumor in one area. It often can’t treat
cancer that has spread.
Types of Conventional Surgery
Palliative surgery
Improving quality of life for patients with advanced cancer or widespread disease.
Relieve pain or restore physical function when a tumor causes pressure or blockage in
the body.
Prevention
• Some surgery is performed to reduce the risk of developing cancer.
• Eg. women with a strong family history of breast or ovarian cancers or known mutations
to the BRCA1 and BRCA2 breast and ovarian cancer genes may decide to have a
mastectomy or oophorectomy to lower the risk of developing breast or ovarian cancer.
Types of Therapies

Minimally Invasive Surgery
•Instead of one large cut, the surgeon makes several small ones and puts a tube
with a tiny camera into one cut to see inside our body, and tools into the others.
Minimally invasive surgeries are:
 Laser surgery- The use of a narrow beam of high-intensity light to remove
cancerous tissue.
 Cryosurgery- The uses liquid nitrogen or argon gas to freeze and kill abnormal
cells.
 Mohs micrographic surgery- dermatologist shaves off a skin cancer, one layer at
a time, until all cells in a layer appear to be normal cells when viewed under a
microscope.
 Endoscopy- A thin, flexible tube with a light and camera is inserted into the
body. This device is called an endoscope. During this procedure, it is possible to
remove samples of potentially abnormal tissues.
 Photodynamic therapy is a laparoscopic surgery that puts drugs near tumors.
Light activates the medicine, and it kills cancer cells.

CHEMOTHERAPY
•Chemotherapy uses drugs to kill cancer cells. There are over 100 different types of
chemo drugs.
•This strong medication keeps cancer from spreading, makes it grow slower, or even kills
cancer cells.
Chemotherapy drugs can:
•Impair mitosis, or prevent cell division.
•Trigger the suicide of cancer cells (apoptosis).
• Stop the growth of new blood vessels that supply a tumor in order to starve it.
•It can cause side effects, as it also kills fast dividing cells including those in our
blood, mouth, digestive system, and hair follicles.
1. Alkylating agents- Work directly on the DNA and kill the cells at different stages of the
cell life cycle. Eg: chlorambucil, cyclophosphamide.
2. Antimetabolites- Mimic proteins that the cells need to survive. Eg: 5-Fluorouracil (5-
FU), Gemcitabine (Gemzar®).
3. Plant alkaloids- Block the ability of the cells to grow and divide. Eg: Paclitaxel and
docetaxel.

RADIATION THERAPY
Radiation therapy uses high doses of radiation to kill cancer cells and shrink tumors.
Ionizing radiation used in cancer therapy.
External Beam Radiation
•The beam of radiation is focused by an external machine onto the treatment area.
•Use x-rays / gamma rays, or a combination to kills or damages cells.
Internal Radiation
•Radioactive implants about the size of a grain of rice is put inside the body where the
tumor is located. The radiation kills the cancer cells.
•This treatment makes us radioactive for a while, so it is advised to avoid other people
until it’s finished. This is also known as brachytherapy
HORMONE THERAPY
• Hormone therapy is a form of targeted drug therapy that slows or stops the growth of
cancer that uses hormones to grow.
•Hormone therapy stops hormones being made or prevents hormones from making
cancer cells grow and divide.
Hormone therapy may be given :Oral, Injection, Surgery.
Eg. Tamoxifen, goserelin (Zoladex).

PRECISION MEDICINE
•Precision medicine is an approach to patient care that allows doctors to select
treatments that are most likely to help patients based on a genetic understanding of
their disease.
•To figure out which genetic changes are in your cancer, you may need to have a
biopsy.
•Genetic changes in cancer discovered by DNA sequencing, genomic testing,
molecular profiling, or tumor profiling.
•Once genetic changes are discovered, another active area of research involves
looking for drugs that can target these changes, then testing these drugs with people
in clinical trials.
•Even though researchers are making progress every day, the precision medicine
approach to cancer treatment is not yet part of routine care for most patients.
TARGETED GENE THERAPY
•Gene therapy is the definitive therapeutic practice involving the transferring of DNA
or RNA directly to in vivo cells, or to isolated cells followed by reinfusion of these cells
into human body.
•Gene therapy is a promising approach towards cancer treatment. The main aim of
the therapy is to destroy cancer cells, usually by apoptotic mechanisms, and
preserving others.

IMMUNOTHERAPY
Cancer immunotherapy uses our own immune system to fight the cancer. It either
boosts our immune system or marks cancer cells so our immune system can see and
destroy them more easily.
This can be done in different ways:
Stimulating own immune system to work harder or smarter to attack cancer cells
Administration of immune system components, such as man-made immune system
proteins.
Main types of immunotherapy
•Monoclonal antibodies: They mark cancer cells for immune system to attack. They can
also help chemotherapy and radiation go directly to cancer cells.
•Immune checkpoint inhibitors: These drugs basically take the ‘brakes’ off the immune
system, which helps it to recognize and attack cancer cells.
•Cancer vaccines: Vaccines are substances put into the body to start an immune
response against certain diseases. Some vaccines can help to prevent or treat cancer.
eg. HPV Vaccines ,Sipuleucel-T for prostate cancer

Cancer develops when the body’s immune system fails to attack tumor cells. Allison
wondered whether blocking the blocker the CTLA-4 molecule would set the immune
system free to destroy cancer
In 1996, Allison published a paper showing that antibodies against CTLA-4 erased tumors
in mice.
The job of getting anti–CTLA-4 into people fell to a small biotechnology company,
Medarex, in Princeton, New Jersey. It acquired rights to the antibody in 1999 and were
the first to use it as a drug.
James P Allison’s discoveries built on 1980s who were studying
Tcells, components of the immune system that attack cells that
the body recognizes as foreign.
They identified a key receptor on the surface of T cells - cytotoxic
T-lymphocyte antigen 4(CTLA-4). The receptor puts the brakes on
T cells, preventing them from launching full-out immune attacks.
2018 NOBEL WINNERS IN MEDICINE

Tasuku Honjo, meanwhile, in the early 1990s discovered a
molecule expressed in dying T cells, programmed death 1
( PD-1); he recognized PD-1 as another brake on T cells.
The first clinical trials using PD-1 were even more dramatic
than those with CTLA-4. Several patients with metastatic
cancer were apparently cured. And side effects seemed
milder than those observed with CTLA-4 therapies.
drugs:Nivolumab,pembrolizumab.

•Eating a healthy diet.
•Exercising regularly.
•Limiting alcohol.
•Maintaining a healthy weight.
•Minimizing your exposure to radiation and toxic chemicals.
•Not smoking or chewing tobacco
•Reducing sun exposure, especially if you burn easily
PREVENTION

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