Conventional Treatment for Cancer

Conventional
Treatments
for
Cancer

The conventional approach to treat cancer is to:
● Cut it - Surgery
● Burn it - Radiotherapy
● Poison it - Chemotherapy
When a cancer is localised, it can be removed by surgery. But in most of the cases, it is
practically impossible to detect cancer in such an early stage. The cancerous cells do get
killed by chemotherapy and radiotherapy, but both of these therapies also destroy some vital
cells in the body, leading to serious side effects. It is extremely difficult for scientists to
prepare a drug that could kill the cancerous cells selectively without harming normal cells of
the body. Another major drawback of chemotherapy is drug resistance. Moreover,
recurrences are commonly seen after chemotherapy and radiotherapy. Other conventional
techniques used in the treatment of cancer including bone marrow transplantation,
peripheral stem cell transplantation, hormone therapy, photodynamic therapy,
immunotherapy and gene therapy have their own limitations.

In many cases, surgery offers the best chance of getting rid of the disease, especially if it hasn’t
spread to other parts of the body and causes fewer side effects. But chemotherapy is still sometimes
the best option for a patient as chemotherapy uses drugs to kill cancer cells. Whereas, Radiotherapy
treatment uses high-energy particles or waves to destroy or damage cancer cells to keep them from
spreading. It might be your only treatment, or you might get it along with surgery or chemotherapy.
Most Common Treatments for cancer

1. Radiotherapy
In radiotherapy, therapeutic doses of radiation (which are many times higher than the
diagnostic doses) are used to kill the cancerous cells. A single large dose of radiation may
kill the cancerous cells, but it will also burn the adjoining healthy tissues. Therefore, the
required doses of radiation are usually fractionated into smaller doses, however, damage to
the healthy tissue still occurs. Radiotherapy has proved more effective in the treatment of
tumours of the food pipe, testes and the brain.
The history of radiotherapy goes back to 1895 when Wilhelm Conrad Roentgen discovered
X-rays for diagnostic purposes. Two years later, in 1897, it was disclosed in a meeting of the
Vienna Medical Society that a mole has disappeared after repeated exposures to the X-rays.
Since then, X-rays have been used to treat various tumours. Later, during the 1950s, an
artificial radioactive isotope of cobalt was developed that delivered radiation deeper into the
body as compared to the X-rays. These were named gamma rays, which were similar to X-
rays except that these have a shorter wavelength.

The X-rays and gamma rays are almost outdated now and their place has been taken up by
the high-energy electron beam generated by linear accelerators. In the past, the doses of
radiation were used to be measured in rad (radiation absorbed dose), but this unit has
recently been replaced by gray (1 Gy = 100 rad). Radiotherapy can be given internally or
externally.
● Internal Radiotherapy
In internal radiotherapy, the radioactive implant (a sealed container of radioactive substance)
is placed directly into the tumour or in one of the body cavities. The radioactive implant is
usually kept in the body for 1 to 7 days but sometimes it is implanted permanently. In the
afterloading technique of internal radiotherapy, an empty container is first placed in the body
and then the radioactive substance is inserted into it. In some patients, the radioactive
substance (in the liquid form) is administered orally or by injection. There are three different
techniques for giving internal radiotherapy. These are intracavitary radiotherapy, interstitial
radiotherapy and brachytherapy.

● External Radiotherapy
In external radiotherapy, the X-rays and the gamma rays have been used extensively to
treat cancer. The X-rays generate extranuclear radiation, whereas the gamma rays generate
intranuclear radiation but both of these are ionising radiations, which form highly reactive
ions in the exposed cells. The use of X-rays and gamma-rays in radiotherapy is now
replaced by the high-energy electron beam (generated by linear accelerators) that can be
focused on a smaller area, thus minimising the damage to the adjoining tissues.
In the hyper fractionated technique of external radiotherapy, smaller doses of radiation are
given throughout the day instead of a single large dose. In the super fractionated technique
of external radiotherapy, smaller doses of radiation are given many times in a day, but the
total combined dose of radiotherapy is greater than that of the single daily dose. The effect
of radiotherapy can be enhanced by using hyperbaric oxygen and hyperthermia techniques.

● Radioimmunotherapy
Radioimmunotherapy is a new technique of radiotherapy that delivers radiation directly to the
cancerous cells. In this technique, first of all, the specific antibodies produced in the patient’s
body against some components of the cancerous cells are collected from the patient’s blood.
Later, a radioactive isotope is attached to these antibodies in the laboratory. These
antibodies carrying the radioactive isotope are then injected back to the patient, which travel
through the bloodstream to reach the cancerous cells and get attached to them. By this
technique, the radioactive isotope is directly delivered to the cancerous cells that kill them
selectively, thus sparing normal cells of the body from the damaging effect of radiotherapy.
The cancerous cells exist in the body in three different forms, i.e. dividing cells, dying cells
and dormant cells. Radiotherapy can kill the dividing cancerous cells. The dormant cells do
survive even after exposure to the radiotherapy. These dormant cancerous cells may get
back into the cell cycle after some time and multiply to produce many more cancerous cells
that may form the cancerous growth again.

Such a cancerous growth, which reappears at the same site (or any other site in the body),
from where the original cancerous growth apparently disappeared after administration of
radiotherapy, is known as recurrence.
There are various side effects of radiotherapy such as nausea, vomiting, dryness of mouth,
difficulty in swallowing, change or loss of taste, earache, cough, frequency of urination,
diarrhoea, change in the texture of the skin, loss of hair, sterility and decreased blood cell
counts.

2. Chemotherapy
In chemotherapy, the cytotoxic drugs are used to kill the cancerous cells. This therapy is
preferred when surgery or radiotherapy is not possible. The history of chemotherapy is
rather unusual. A toxic chemical compound known as Sulphur Mustard (that causes burns in
the skin, respiratory tract and eyes) was developed and used as a chemical weapon during
the World War II. It was observed that Sulphur mustard also decreased the blood cell counts
by destroying stem cells in the bone marrow. The research continued on Sulphur mustard
and later its derivative known as Nitrogen mustard was developed, which was the first
cytotoxic drug, ever used to treat cancer. Since then many cytotoxic drugs have been
developed and used in the treatment of cancer including antimetabolites (such as
Methotrexate), alkylating agents (such as Cyclophosphamide), antibiotics (such as
Adriamycin), plant alkaloids (such as Vincristine), nitrosoureas and many other
miscellaneous compounds.

Chemotherapy is usually given intravenously. It can be given by intramuscular, intra-arterial,
intrathecal and oral administration. Sometimes the chemotherapeutic drugs are injected into
the body cavities such as pleural cavity and peritoneal cavity. The doses of
chemotherapeutic drugs are repeated at weekly, fortnightly, three-weekly or monthly
intervals depending on the combination of the drugs.
● Regional Chemotherapy
Regional chemotherapy is a technique of chemotherapy that delivers chemotherapeutic
drugs to a particular part of the body. This technique helps to increase the anticancer effect
of drugs at the site of cancer. It also minimises the toxic side effects of the chemotherapy on
other parts of the body.
● Regional Perfusion
Regional perfusion technique of chemotherapy, in which the chemotherapeutic drugs are
delivered directly to the cancerous tissue, is usually preferred to treat the cancers located in
the upper and lower extremities.

● Chemoembolisation
Chemoembolisation is another technique, which is proving successful, particularly in the
treatment of liver cancer. In chemoembolisation, the cytotoxic drugs are delivered directly to
the affected organ through a catheter along with another agent that slows down blood flow to
the organ.
Chemotherapeutic drugs are capable to kill the cancerous cells during a particular phase of
the cell division. At any given time, the cancerous cells are asynchronous, i.e. in different
phases of the cell cycle. A specific chemotherapeutic drug that is capable to kill the cells in S
phase may not harm the cells in G1, G2 and M phase. To overcome this problem, multiple
drug therapy is used, in which various chemotherapeutic drugs are added in the treatment
plan.
Cancerous cells may become resistant to the drugs used in chemotherapy. The drug
resistance may be intrinsic or acquired. In intrinsic drug resistance, the currently available
drugs used in chemotherapy have no effect on specific cancer as seen in the malignant
melanoma and the renal cell carcinoma.

The acquired drug resistance is developed in the cancerous cells due to gene amplification.
Multi-drug resistance (MDR) is also seen in chemotherapy. MDR occurs due to excessive
production of P-glycoprotein (also known as pump protein), which pumps out the
chemotherapeutic drugs from the cancerous cells.
Chemotherapy leads to various side effects such as nausea, vomiting, loss of appetite,
constipation, diarrhoea, ulcers in the mouth and loss of hair. Most of the cytotoxic drugs
used in chemotherapy destroy the bone marrow cells leading to decreased blood cell counts.
Such patients are highly susceptible to infections and need frequent blood transfusions. The
administration of colony-stimulating factors (CSF) restores the bone marrow functions in a
shorter period by stimulating the growth of the bone marrow cells. The colony-stimulating
factors are specific proteins that are normally produced in the human body.

3. Hormone Therapy
Tumours originating in the hormonal dependent organs (such as the breast, prostate,
endometrium and the thyroid) may retain the hormonal dependency. Hormone therapy is
effectively used in the treatment and palliation of such cancers. Hormone therapy may be
given by various modes including hormonal medication, surgical removal of the hormone-
producing glands (such as orchidectomy, oophorectomy and adrenalectomy) and by
destroying the hormone-producing glands with radiotherapy.Some breast cancers need
oestrogen for their growth. An anti-estrogen compound known as Tamoxifen is used in the
treatment and palliation of such cancers of the breast. Sometimes, oophorectomy is done to
arrest the growth of hormone-dependent breast cancers.
● Megestrol acetate is a progestin hormone, which is used in the treatment of the
hormone-dependent breast carcinoma.
● Medroxyprogesterone is another progestin hormone, which is used in the treatment of
endometrial carcinoma.

● Fluoxymesterone is an androgen hormone, which is used in the treatment of the
hormone-dependent breast carcinoma.
● Oestrogen arrests the growth of prostate cancer. Diethylstilbestrol (DES) is an
oestrogen hormone, which is used in the treatment of disseminated cancer of the
prostate.
● Flutamide and Cyproteron are antiandrogens, which are used in the treatment and
palliation of disseminated cancer of the prostate.
● Leuprolide and Buserelin are GnRH agonists. These are used in the treatment of
disseminated cancer of the prostate.
● Orchidectomy (surgical removal of the testis) is done to arrest the growth of prostatic
cancer. Orchidectomy helps by stopping the production of testosterone.
● Aminoglutethimide is an aromatase inhibitor hormone, which is used in the treatment
and palliation of metastatic breast carcinoma and disseminated cancer of the prostate.
● Octreotide is a somatostatin analogue, which is used in the treatment and palliation of
metastatic carcinoid tumours & vasoactive intestinal polypeptide secreting tumours.

● Thyroid hormone is used in the treatment and palliation of papillary carcinoma of the
thyroid.
● Adrenal steroids are used in the treatment of non-endocrine related tumours, for
example, prednisolone is used in the lymphatic leukaemia, methylprednisolone in the
lymphomas and dexamethasone in the breast carcinoma.
Hormone therapy is effective if the tumour contains cytoplasmic hormone receptors such as
the oestrogen receptors and the progesterone receptors. The hormone receptors are
assayed by the tissue biopsy and by the metastatic lymph node biopsy. The side effects of
hormone therapy may be observed but these are usually less severe as compared to that of
the chemotherapy.

Hormonal therapy is a treatment that adds, blocks or removes hormones to slow or stop the growth of
cancer cells that need hormones to grow. Hormonal therapy is also called hormone withdrawal therapy,
hormone manipulation or endocrine therapy. Hormone therapy is effective in tumours that have either
oestrogen or progesterone receptors, or both to block the effect of oestrogen in the breast cancer cell.
Hormonal therapy works on hormone positive breast cancer.
How does Hormone-therapy works in breast cancer?

4. Bone Marrow Therapy
In the bone marrow transplantation (BMT), the patient’s bone marrow is replaced by healthy
bone marrow of the matching donor. BMT is usually recommended to the advanced cases of
leukaemia, non-Hodgkin’s lymphoma and multiple myeloma. The technique of bone marrow
transplant was first developed in the 1950s. Bone marrow transplantation is of three types,
i.e. syngeneic, allogeneic and autologous. In syngeneic bone marrow transplantation, the
donor is a perfect match to the patient, which is possible only in the identical twins. In
allogeneic bone marrow transplantation, the donor is the closest match to the patient. Six
markers, known as human leukocyte antigens (HLA), which are found on the surface of the
white blood cells are considered while selecting a donor for the bone marrow
transplantation. In autologous bone marrow transplantation, the patient’s own bone marrow
is harvested and then given back to the patient when required, for example after intensive
chemotherapy.
Autologous bone marrow transplantation is usually advised in those patients of acute
leukaemia and the high-grade lymphoma, who have achieved good remissions.

While performing BMT, bone marrow of the patient is first destroyed by giving high doses of
chemotherapy or radiotherapy. Thereafter the bone marrow collected from the matching
healthy donor (or harvested bone marrow of the patient) is injected to the patient
intravenously, just like an ordinary blood transfusion. The injected bone marrow cells reach
the bone marrow of the patient and get grafted there and start functioning within 2 to 4
weeks. This period of engraftment is very critical, during which the patient is kept in a germ-
free room till the grafted bone marrow cells start their normal functioning. The bone marrow
transplantation has its own complications such as rejection and graft versus host disease.
● Peripheral Stem Cell Transplantation
Peripheral stem cell transplantation, also known as haematopoietic progenitor cell
transplantation (HPCT), is done in cancer patients to reconstitute the bone marrow. It is
usually recommended to the patients of leukaemia, lymphoma and the multiple myeloma.
Stem cells are primitive haematopoietic cells, which form mature cells of the blood. These
are found in the bone marrow, umbilical cord blood and the peripheral blood. Stem cells are
capable of self-renewal and differentiation.

Peripheral stem cell transplantation is of three types, i.e. syngeneic, allogeneic and
autologous. Autologous peripheral stem cell transplantation is the most popular technique, in
which stem cells from the peripheral blood of the patient are separated by a technique called
pheresis. The separated stem cells are then frozen and stored, to be reinfused to the same
patient at a later stage, when the bone marrow of the patient gets destroyed with
chemotherapy. Peripheral stem cell transplantation has a shorter recovery period as
compared to bone marrow transplantation. Complications of the peripheral stem cell
transplantation include graft versus host disease and veno-occlusive liver disease.

How does Bone Marrow Therapy works?

5. Immunotherapy
The immune system of the body executes its work by two different modes, known as
antibody-mediated immunity (humoral immunity) and cell-mediated immunity. The antibody-
mediated immunity works through B-lymphocytes, which produce specific antibodies in
response to the bacteria, viruses and the toxic molecules that enter the human body. Cell-
mediated immunity operates through the cytotoxic T lymphocytes (CTL), natural killer cells
(NK cells), lymphokine-activated killer cells (LAK cells) and the macrophages. Cell-mediated
immunity empowers the immune cells to eliminate viruses, bacteria and other pathogens
from the body, either physically (by engulfing) or by secreting specific chemicals. It is the
cell-mediated immunity that protects the human body from cancer.
Immune cells of the body produce certain biologically active substances known as cytokines
(lymphokines and monokines), which include interleukins (IL-1 to IL-15), interferons (alpha,
beta and gamma), tumour necrosis factors (TNF) and colony-stimulating factors (CSF).
Cytokines are capable to destroy cancerous cells by stimulating the effector cells, i.e.
cytotoxic T lymphocytes (CTL), natural killer cells (NK cells) and lymphokine-activated killer
cells (LAK cells).

Researchers all over the world have been working on different techniques to enhance the
immune system of the body to fight cancer for more than 100 years. During this period,
scientists have attempted specific and non-specific methods of immunotherapy in the
treatment of cancer. Certain natural and synthetic substances have been used to restore or
boost the immune system of the body. Tremendous progress has been made in
immunotherapy since the early 1970s, although there is still a long way to go. Alpha
interferon was made by recombinant DNA technology in 1981 and has been used since then
in the treatment of cancer. Monoclonal antibodies are under trial in the treatment of cancer
since the 1980s.

How does Immunotherapy works?
(1)
T-cells are a type of immune
cells which protects body from
the infection. They destroy
virally infected cells.
(2)
Cancer cells produce a
molecule which stops T-cells
from recognising the cancer
cells as a threat - allowing the
cancer to grow.
(3)
The drug used in immunotherapy
attaches itself to T-cells blocking the
cancer’s ability to hide. Cancer cells
are then attacked and destroyed.

6. Gene Therapy
Scientists are trying to replace the defective or missed genes by normal genes in the
initiated, mutated and the cancerous cells in the prevention and treatment of cancer.
Immune cells of the body can be altered genetically to arm them with cancer-fighting genes.
Another approach in gene therapy is to alter the cancerous cells genetically and use them as
a cancer vaccine to enhance the immune response of the body against cancer.
Dr Steven Rosenberg of the National Institute of Health, USA, was the first to carry out gene
therapy. He collected tumour-infiltrating lymphocytes (TILs) from cancerous growth of the
patient and inserted the gene of tumour necrosis factor (TNF) in these TILs. He then
multiplied the tumour-infiltrating lymphocytes (containing tumour necrosis factor) in culture
and injected them back to the patient. By this procedure, Dr Steven Rosenberg was
successful in delivering the genes of tumour necrosis factor directly to the cancerous cells,
thus killing them selectively without harming normal cells of the body.

Cancerous cells can be nipped in the bud with a new gene therapy, developed by scientists
at Jefferson Medical College in Philadelphia, Pennsylvania, who focused on a gene called
FHIT, which is located on the human chromosome 3. The disappearance of the FHIT gene is
regarded as the earliest genetic signal indicating that the cell is about to become cancerous.
Modified viruses carrying spare copies of FHIT gene are used to prevent the onset of
cancer.

7. Photodynamic Therapy
Photodynamic therapy or Phototherapy was previously known as photoradiation therapy.
The photodynamic process was first reported in 1900 by a German scientist, who discovered
that microorganisms could be inactivated by certain dyes in the presence of light.
Photodynamic therapy was first tried on cancer patients in the 1960s. In photodynamic
therapy, a photosensitizer called Photofrin is injected to the patient that gets concentrated in
the cancerous cells. The tumour is then exposed to a laser beam, using a fibre-optic probe.
The laser beam activates the Photofrin leading to a toxic reaction that kills cancerous cells.
Photodynamic therapy kills the cancerous cells selectively without harming normal cells of
the body. Photodynamic therapy is used in the treatment of superficial tumours and those
tumours that can be approached by an endoscope including cancers of the lung,
oesophagus, bladder and the female pelvis. Photodynamic therapy has its limitations
because the laser beam does not penetrate more than one centimetre of tissue. The side
effects of photodynamic therapy include skin sensitivity reaction (leading to severe sunburns
on exposure to the sunlight), the sensitivity of the eyes to light, local pain, nausea, vomiting,
metallic taste and liver toxicity.

How does Photodynamic Therapy works?
Photodynamic therapy treats premalignant growths by using special drugs called photosensitizing
agents, along with light, to kill precancerous cells. The drugs only work after being activated by certain
wavelengths of light. The process also is known as PDT, photoradiation therapy, phototherapy and
photochemotherapy.

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Conventional Treatment for Cancer

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