CANCER: A COMPREHENSIVE
REVIEW
Jayesh M. Rajput
JES’s college of Pharmacy, Nandurbar, Dist Nandurbar, MS, India.
Abstract: Cancer
is a multifactorial, heterogeneous and chronic disease. Basically, cancer
itself is a group of diseases, because of its frequency, reciprocal
influences-even minor influence may lead to a major impact. Epidemiological
studies clearly indicate thatrisk for several types of cancer (including
pancreas cancer, liver cancer, breast cancer, urinary tract (colorectal)
cancer is too high for mortality and morbidity. Obesity, hyperglycemia, and
increased oxidative stress may also contribute to increased cancer risk.
Despite many decades of basic research and clinical research and trials of
promising new therapies, new drugs, new treatments, cancer is the main
cause of morbidity and mortality. In conclusion cancer is a complex disease
which is gaining more of its popularity in humans and so, it needs more
clinical attention and better designed treatments, studies and drugs.
Keywords: Cancer, Oncogenes, Leukemia
Key
Words:
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Article History
Received: 15/12/2022
Revised: 21/12/2022
Accepted: 27/12/2022 Published: 01/01/2023
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INTRODUCTION
Cancer is a broad term; it is the disease
which results when the cellular changes cause uncontrolled growth and division
of the cells.[1,3,8,9] In simple terms, cancer is a group of more
than 100 diseases that develops across time and involve the uncontrolled body
cells. Cancer is a disease that can develop in any of the body tissue and from
that each of the cancer type consists of its unique features, cancer begins
when a cell breaks free from the normal restraints on cell division and begins
to follow its own proliferation.
[1,2,3]
The name cancer derives from an
observation by “Hippocrates” more than 2,300 years ago. The term “Korkinoma”,
in Greek came then later, Cancer in Latin. The Hooke in 1600s, and Virchow in
1800s, came to an observation that the living tissues are composed of cells and
all the cells arise as direct descendants of other cells. This understanding
has raised more questions about cancer. [1,5,10,16] one of the
important observations from early were made in 1775, an incidence of scrotal
cancer was spread among workers who worked as chimney sweeps as boys, and in
the mid of 1800s, lung cancer was observed at alarmingly in high rates among
the pitch blende miners in Germany.And by the end of the 19th
century using cigarettes, cigars were thought by some physicians to be closely
associated with cancers of the mouth and throat. These kind of observations and
other observations too suggested that the origin and cause of cancer may lie
outside the body and more important that cancer could be linked to identifiable
and even preventable causes. [2,8] The 30 trillion cells of the
normal, healthy body live in a complex regulating one another’s proliferation.
The normal cells reproduce only when they get instructed to do so by other
cells, such unceasing collaboration ensures that each tissue maintains a size
and architecture appropriate to the body’s needs. [1,3] Cancer cells
violate this scheme, they become deaf to the usual controls on proliferation
and follow their own re-production agenda. [2] Tumors composed of
such malignant cells and becomes more and more aggressive over time, and they
become lethal when they disrupt the tissues and organs needed for the survival
of the organism as a whole. Scientists have discovered set of some basic
principles which governs the development of cancer that the cells in tumor
descend from a common ancestral cells that at one point-usually decades before
a tumor becomes palpable, initiated a program of the inappropriate reproduction, then the
malignant transforms of a cell comes about through accumulation of mutations in
specific classes of the genes within it.These genes provide the key to
understand the process at the root of human cancer. Gene that are carried out
in the DNA molecules of the chromosomes in cell nucleus. A gene specifies a
sequence of amino acids that must be linked together to make particular
protein; the protein then carries out the work of the gene, and when the gene
is switched on then the cell responds by synthesizing the encoded protein.
Mutations in a gene can perturb a cell by changing the amount or the activities
of the protein product. Two of the gene classes, which together constitute only
a small proportion of the full genetic set, which plays amajor role in
triggering the cancer. The development of tumor occurs in three main stages
first a genetically altered cell their tumor development begins when some cells
within a normal population sustains a genetic mutation that increases its
propensity to proliferate when it would normally rest. Then the second stage is
called as hyperplasia where the altered cells and its descendants continue to
look normal, but they re-produce too much-after years, one in a million of
these cells suffers another mutation that further loosens controls on cell
growth then the final stage is dysplasia where the off-spring of the cell
appear abnormal in shape and in orientation; the tissue is now said to exhibit
dysplasia once again, after a time a rare mutation that alters cell behavior
occurs. Then after these three stages cancer or in-situ cancer begins to
develop from the fourth stage where the affected cells become still more
abnormal in growth and appearance. If the tumor has not broken into tissues,
then it is called as in-situ cancer. This tumor may remain contained
indefinitely, however, some cells may eventually acquire additional mutations,
then in the fifth stage if the genetic changes allows tumor to perform invading
underlying tissue and to shed cells into the blood or lymph, the mass is
considered to have become malignant. The renegade cells are likely to establish
new tumors (metastases) in the body; these may become lethal by disrupting a
vital organ.
Some genes involved in human Cancers
[1.2,3,8] Genes are known as proto-oncogenes code for
proteins whichstimulates the cell division; mutated forms, called oncogenes,
can cause the stimulatory proteins to be over-active, with the result that
cells proliferate excessively. Tumor suppressor genes code for proteins that
inhibit the cell division. Mutations can cause the proteins to be inactivated
and may thus deprive cells of needed restraints on proliferation. Investigators
are still trying to decipher the specific functions of many tumor softener
genes.
Table 1: Tumor Softener
genes
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·
Genes for proteins in the Cytoplasm
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1)
APC
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Involved
in colon and stomach cancers
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2)
DPC 4
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Codes for a
relay molecule in a signaling pathway that inhibits cell division, involved
in pancreatic cancer
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3)
NF-1
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Codes
for a protein that inhibits a stimulatory (Ras) protein. Involved in
neurofibroma and pheochromocytoma (cancers of the peripheral nervous system)
and myeloid leukemia
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4)NF-2
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Involved in
meningioma and ependymoma (brain cancers) and schwannoma (affecting the
wrapping around peripheral nerves)
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|
·
Genes
for proteins in the nucleus
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|
1)
MTS 1
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Codes for the
p16 protein, a braking component for the cell cycle clock, involved in a
broad range of cancers
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2) RB
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Codes
for the pRB protein, a master brake for the cell cycle, involved in
retinoblastoma and bone, bladder, small cell lung and breast cancer
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3)
P53
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Codes for the
P53 protein, which can halt cell division and induce abnormal cells to kill
themselves, involved in a wide range of cancers
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4) WT
1
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Involved
in Wilms “Tumor of the kidney”
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·
Genes
for proteins whose cellular location is not yet clear
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1)
BRCA 1
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Involved
in breast and ovarian cancers
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2)
BRCA 2
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Involved in
breast cancer
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3)
VHL
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Involved
in renal cell cancer
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Table 2: Oncogenes.
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·
Genes for the growth factors or their receptors
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|
1)
PDGF
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Codes
for platelet-derived growth factor, involved in glioma (a brain cancer)
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2)
erb-B
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Codes for the
receptor for epidermal growth factor, involved in glioblastoma (a brain
cancer) and breast cancer
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3)
erb-B2
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Also
called HER-2 or nev. codes for a growth factor receptor, involved in breast,
salivary gland and ovarian cancers
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4)
RET
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Codes for a
growth factor receptor, involved in thyroid cancer
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·
Genes
for cytoplasmic relays in stimulatory signaling pathways
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|
1)
Ki-ras
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Involved in lung
cancer, ovarian cancer, colon cancer and pancreatic cancers
|
|
2)
N-ras
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Involved
in leukemias
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·
Genes
for transcription factors that activates growth-promoting genes
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|
1)
C-myc
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Involved
in leukemias and breast cancer, stomach cancer and lung cancer
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2)
N-myc
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In neuroblastoma
(a nerve cell cancer) and glioblastoma
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3)
L-myc
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In
lung cancer
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·
Genes
for some other kinds of molecules
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1)
BCL2
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Codes
for a protein which normally block cell suicide, involved in follicular B
cell lymphoma
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2)
BCL1
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Called as PRAD1.
Codes for cyclin D1, a stimulatory component of the cell cycle clock,
involved in breast cancer, head cancer and neck cancer
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3)
MDM-2
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An
antagonist of the p-53 tumor suppressor protein, in sarcomas (connective
tissue cancers) and other cancers
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Types
of Cancers
There
are multiple types of cancers today but, some of the common types of cancers
are: [2,8,14,15,16,19]
·
Bladder
cancer
·
Thyroid
cancer
·
Breast
cancer
·
Prostate
cancer
·
Colon
and Rectal cancer
·
Pancreatic
cancer
·
Endometrial
cancer
·
Non-Hodgkin
Lymphoma
·
Kidney
cancer
·
Melanoma
·
Lung
cancer
·
Liver
cancer
·
Leukemia
·
Skin
cancer
Basically, cancer is named after the part
of that particular body from which it is originated.
For example:if kidney cancer spreads to
the lungs, that time it is still known as kidney cancer not lung cancer in this
case lung cancer would be an example of a secondary tumor. Caner is not just
one disease it isa group of diseases, all of which causes cells in the body to
change and grow out of control.
Categories
of Cancer
There
are five broad categories which indicates the tissue and blood classifications
of cancer. [1,2,8,15,16]
1)
Carcinoma: It is the cancer which is found in the tissue known as “Epithelial
tissue”that covers surfaces of organs, glands, or body structures and there
are four main types of carcinomas they are Melanoma, Basal cell carcinoma,
Squamous cell skin cancer and Merkel cell carcinoma.
2)
Sarcoma: It is a malignant tumor growing from connective tissues, such as
cartilage, fat, muscles, tendons and bones. Most common sarcoma is of bone,
example- osteosarcoma (occurs in bone) and chondrosarcoma (occurs in
cartilage), there are somefour types of sarcomas they are soft tissue sarcoma,
osteosarcoma, chondrosarcoma and Ewing’s sarcoma.
3)
Lymphoma: The cancer that originates in the nodes or glands in the lymphatic
system, there are three types of lymphoma they are Hodgkin’s lymphoma,
non-Hodgkin’s lymphoma and Cutaneous lymphoma.
4)
Leukemia: Also called as “Blood Cancer” or cancer of bone marrow, that keeps
bone marrow from producing normal red and white, blood cells and platelets.
Types of leukemia includes Acute lymphocytic leukemia, Acute myeloid leukemia,
Agnogenic myeloid leukemia, Chronic myeloid leukemia, Essential thrombocythemia
(ET), Hairy cell leukemia and Myelodysplastic syndromes (MDS).
5)
Myeloma: It grows in the plasma cells of bone marrow; in some cases, the
myeloma cells collect in one bone and forms a single tumor that is called a
plasmacytoma. However, in some other cases, the myeloma cells collect in many
bones, forming many bone tumors, that is called multiple myeloma.
Causes
of Cancer
There
is not a single cause of cancer. Researchers believes that it is the
interactivity of multiple factors together that generates the cancer. The
factors maybe environmental, genetic or many others. The overall five-year
survival rate for childhood cancer is about 80%, while in adult’s cancers the
surviving rate is 68%, as per researchers there are many and repetitive risk
factors or exposures, which includes: [2,5,9,17,21,24]
o
Genetic
disorders: for example, Wiskott-Aldrich and Beckwith-Wiedemann syndrome
alsocalled to change the immune system. One another theory suggests that cell
in the stem cells, bone marrow becomes damaged, so when they replicate to make
more cells, they make abnormal cells which are also known as cancer cells.
o
Genetics,
Inheritance and Family historymay play an important role in childhood cancers.
o Lifestyle factors: such as smoking, a high-fat diet
and working with some of the toxic chemicals are examples of lifestyle choices
that may berish factors for some adult cancers. Most children with cancer.
How Cancer is diagnosed?
There is not a single/ specific test to
diagnose cancer. Many tests are needed to find out whether a person has cancer,
or if any other condition or an infection is imitate the symptoms of cancer. [2,6,15,16,17,23]
The complete evaluation of a patient requires a throughout history and
physical examination along with diagnostic testing. Effective testing for
diagnosis is used to confirm and eliminate the presence of disease, monitor the
disease process and to effectively plan for its treatment. Diagnostic
procedures for cancer may include Laboratory tests, tumor biopsy, imaging,
surgery, endoscopic examinationor genetic testing. Some of the common tests to
check the chemical components in bodily fluids and tissues are blood tests,
(CBC), urinalysis, tumor markers. Diagnostic imaging includes X-rays, computed
tomography scans (also known as CT scans or computer axial tomography or CAT
scan), bone scanning, lymphangiogram (LAG), mammogram. Reflection imaging which
includes ultrasound. Magnetic resonance imaging (MRI). Even there are some
different types of endoscopic examinations used to diagnose cancer which
includes cystoscopy (also called as cystourethroscopy), colonoscopy, endoscopic
retrograde cholangiopancreatography (ERCP), esophagogastroduodenoscopy (also
called as EGD or upper endoscopy), sigmoidoscopy. There are many different
types of tumor biopsies used in the diagnosis of cancer, a biopsy is a
procedure performed to remove tissue or cells from the body for examination
under a microscope. While others need to be done in a hospital. Some biopsies
require use of an anesthetic, to numb the area, while other do not requires any
kind of sedation. It is performed to determine whether tumor is cancerous or to
determine the cause of an inflammation and infection. There are some frequent
types of biopsies they are endoscopic biopsy, excisional or incisional biopsy,
bone marrow biopsy, fine needle aspiration biopsy, punch biopsy, shave biopsy,
and skin biopsy.
How Cancer is treated?
Depending on each person’s medical
history, condition and variety of cancer, the cancer is treated. [1,2,6,7,16,17]
The most repeatedtreatments in today’s world involve chemotherapy and
radiation therapy and some of the other treatments includes surgery and
biological therapies. There are some terms in treatment of cancer and they are:
o
Neoadjuvant
therapy: when doctors choose to use more than one therapy in treating a
patient. Both to neutralize any cancer cells and donate to the efficacy of the
principal therapy.
o
Combined
modality therapy: when doctors choose more than one remedy in treatment of a
patient for example, a combination of radiation and chemotherapy.
o Adjuvant therapy: in this term more than one therapy
in treating a patient. the treatment given after the primary cancer treatment
is completed to improve the chance of a cure for example, sometimes the patient
may be prescribed with multiple treatments.
The common treatments include:
1) Radiation therapy: In this the use of
high-poweremission is used to kill or damage cancer cells, tumors and
non-cancerous diseases, and it also has some disadvantages like side effects.
2) Chemotherapy: The most common treatment
for a cancer nowadays is the chemotherapy. In this the use of anticancer agents
to damage or kill cancerous cells and reduce cancer spreading to other parts of
the body. It too has many side effects such as loss of hairs, tiredness
(fatigue) is more primary side effect of chemotherapy, feeling and being sick,
infections, anemia, bruising and bleeding, sore mouth, loss of appetite, skin
and nail change, memory and concentration problems, sleep problems, sex and
fertility issues, diarrhea and constipation, etc.
3) Hormone therapy: This technique
includes the use of supplemental hormones to prevent or stop the growth or
spread of tumors. And the type of therapy depends upon factors such as age of
patient, the type and size of the tumor, and many of the other factors as well.
4) Bone marrow and blood transplant: This
is a rare and specialized therapy in which transfer of health bone marrow cells
into a patient after their own unhealthy bone marrow has been eliminated.
5) Biologic therapy: Treatments with
substances which are produced naturally in the patient’s own body or which can
be used to block the cancer cells growth.
6) Immunotherapy: Also known as
biotherapy, biological response therapy and biological therapy, is outline to
improvethe body’s immune system or in order to eliminate cancer. The organs,
antibodies and cells of the immune management work to defend and protect the
body against foreign invaders, such as viruses or bacteria. Researchers and
scientists have found that the immune system can both determine the difference
between cancerous cells and healthy cells in the body, and to kill the cancer
cells.
7) Angiogenesis inhibitors: These are the
substances which prevents the formation of blood vessels. In therapy, an
angiogenesis inhibitor prevents the growth of new blood vessels that tumors
need to grow.
CONCLUSION
Long way to go in optimizing the
utilization of these therapies minimizing their complexity and toxicities and
to learn how to integrate them into the current standard of care. Furthermore,
there are many challenges ahead in incorporating them into the healthcare
systems of an economically sustainable manner. Therefore, clinical researchers
are beginning to crisp on managing and predicting these toxicities and
monitoring their long-term outcomes. This may lead to guideline that how to
manage these new therapies and should encourage clinicians to use them as early
as possible in treatment pathways. However, currently not a specific treatment
which for the disease there is a need in today’s world to build a treatment
which can cure the disease without promoting side effects or toxicity and
long-term study are obligatoryfor the novel treatment of cancer.
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