INDEX

CHAPTER TITLE PAGE NO.

NO.

I Abstract and Keywords 1

II Introduction 2

III Cancer prevalence 3

in the world
IV Understanding the 4
cancer
V Causes of Cancer 5

VI Tables and 7
Figures
VII Cancer treatment 9
modalities
VIII Conclusion 20

V Reference 21

KCT’S R. G. Sapkal College of Pharmacy,

Nashik
1. ABSTRACT

Cancer is a global issue majorly affecting developing countries. According to a survey, 63% of deaths due to
cancer are reported from developing countries. There are different conventional treatment modalities that are
available to treat and manage cancer. However, new cancer treatment options are being explored continuously
as over 60% of all current experimental trials worldwide are focusing on tumor cure. The success of treatment
depends upon the type of cancer, locality of tumor, and its stage of progression. Surgery, radiation-based
surgical knives, chemotherapy, and radiotherapy are some of the traditional and most widely used treatment
options. Some of the modern modalities include hormone-based therapy, anti-angiogenic modalities, stem cell
therapies, and dendritic cell-based immunotherapy. This chapter discusses different traditional and novel
treatment modalities to combat different types of cancer.

KEYWORDS

cancer, tumor, radiotherapy, surgical knife, chemotherapy, surgery, immunotherapy, stem cell therapy

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
2.INTRODUCTION
Cancer is a major global issue causing more than eight million deaths annually. Recently, the International Agency
for Research on Cancer (IARC) reported that 7.6 million deaths worldwide were due to cancer. Likewise, 12.7
million new cases are estimated per year[1]. It has been reported that developing countries are at higher risk of
cancer; according to a survey, 63% of cancer-related deaths were reported only from developing countries. Cancer
is a multifactorial disorder involving complex modifications in the genome affected by the interactions between
host and environment. The hallmarks of cancer include independence from growth signals, irresponsiveness to
signals which halt the cell division, uncontrolled replication, evasion of apoptosis, sustained angiogenesis, and
finally the capacity to penetrate in other tissues,
known as metastasis[2]. The microenvironment of benign tumor manifests dysregulation of various regulatory
proteins and extracellular environment which plays a vital role in origination and development of cancers[3].
Before 1950, only surgery was considered as a preferred treatment option for the cure of cancer. After 1960,
radiation therapy was initiated to control local disease. With the passage of time, it was realized that individual
treatment of surgery and radiation is not effective as compared to their use in combination to control the cancer.
Nowadays, drugs, biological molecules, and immune mediated therapies are being used for treatment. Till today,
we have not reached the excepted therapy level that resists the mortality rate and decreases the prolonged survival
time for metastatic cancer. Pathways and characteristics of different tumor entities were determined to create new
revolution in neoplastic cancer or targeting drugs to tumor. Radiation therapy is based upon the use of physical
entities like electrons, protons, and various ions to kill the cancerous cells. The mechanism behind radiation
therapy is that high energy radiations halt the cell division and block their ability to proliferate by damaging their
genetic material. If it is done before surgery, radiation therapy is given with the intention to shrink the tumor. If
done after surgery, radiations will destruct the left behind tumor cells and reduce the cancer relapse[4]. As
radiation therapy acts in a localized manner so to treat systemic cancers, chemotherapy is used alone or in
combination with radiotherapy. Chemotherapy is considered the most effective and extensively used modality in
most types of cancers. Chemotherapy drugs target the tumor cells and mainly produce reactive oxygen species
which largely destroy tumor cells by the means of genotoxicity[5]. However, chemotherapy also harms ordinary
cells that leads to diverse dose dependent side consequences such as fatigue, nausea, hair loss, and vomiting or
even death in extreme cases[6].
A standout among the best cancer treatment modalities is the gene therapy which is direct in situ insertion of
exogenous genes into the tumors which could give a powerful remedial way for the treatment of benign tumors.

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Similarly, hormonal treatments are also widely used for cancer malignancies and generally considered as
cytostatic[7]. Hormonal treatment restricts tumor development by limiting hormonal growth factors. It most likely
acts via the down direction of hypothalamic-pituitary-gonadal axis, blockage of hormone receptor, and restraint
of adrenal steroid synthesis. Strikingly, the use of stem cell therapy is extended beyond regenerative medicine
with increasing knowledge of stem cell behavior. In vitro, stem cells are modified by introducing specifically
customized genes with antitumor effects which create tumor-seeking therapeutic vehicles. Among advanced
cancer treatment modalities, dendritic cell-based immunotherapy is thought to be the most effective treatment
since it manipulates the immune system in a way to destroy tumors without any side effects[8]. This chapter will
provide an ample knowledge about the various types of cancer therapies along with a discussion on their new
trends.

3. Cancer Prevalence in the world

Cancer is the principal cause of death equally in developed and underdeveloped countries but more prevalent
in middle-income countries, probably due to prevailing poor socioeconomic conditions[9]. The geographic
differences in the prevalence of cancer can be explained by many contributing factors, like early diagnosis, age
factor, occurrence of risk factors, screening tests, and accessibility of quality treatment. According to the report
of IARC (International Agency for Research on Cancer), 14.1 million cases of cancers were reported in 2012
globally, of which 8 million were reported from underdeveloped countries that is about 82% of total population
of the world[10].

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
4. Understanding the cancer
Cancer is an abnormal condition in which a group of cells disregard the physiological rules of the cell division
and grow in an uncontrolled manner. Cancerous cells do not respond to the signals that activate the normal cell
cycle because they have a degree of self-sufficiency which leads to the uncontrolled growth and proliferation of
transformed cells[11]. If the proliferation of cancerous cells continues, it can be fatal. In fact, 90% of deaths due
to cancers are because of the spread of cancer cells to other tissues which is called metastasis. During mitosis
normal cells grow in an interdependent manner, relying on the availability of external growth factors. So, when
the supply of these growth signals is limited or terminates, cells cease to reproduce. In contrast, tumor cells grow
independently of any factor or signal [12]. Moreover, normal cells exhibit contact inhibition ability. They cease
cell division in response to the presence of enough number of surrounding cells, i.e., after a particular threshold.
Conversely, cancer cells lack this contact inhibition ability, leading to the formation of unwanted mass of cells
[13]. The life of a normal cell is well-programed; it divides only about 50 times, and then it dies by apoptosis and
is replaced by a new cell. This is in accordance with a limited efficiency of DNA replication, as repeated
replication leads toward shortening of telomeres. Cancer cells, on the other hand, show high activity of telomerase
enzyme that continuously keeps replacing the lost, worn-out ends of telomere, allowing unlimited proliferation
of cells.

4.1. Tumor biology

Cell division, when grows independent of growth factors, forms tumors, which involve a series of steps. In the
very first stage, a large mass of cells known as hyperplasia is formed because of uncontrolled cell division. This
is followed by dysplasia in which cell growth is accompanied with abnormalities. Additional changes occur in
the next stage when these atypical cells start to spread over a limited area of the tissue, losing their original
function. This phase is coined as anaplasia. At this stage, the tumor is not invasive and is considered as benign.
In the advanced stage, the tumor cells acquire the ability to metastasize. They begin to invade the surrounding
tissues as well as those located away via bloodstream. This stage is considered to be malignant and is very hard
to treat. However, not all tumors progress to this level, if identified earlier [14]. Though tumor cells are able to
proliferate independent of growth factors, they still require nutrients and oxygen for their growth. All normal
tissues are sufficiently supplied with capillaries for the supply of nutrients and oxygen to every cell. Similarly,
tumors, as growth progresses, form new blood vessels in a process called as angiogenesis so that nutrients reach
the cells located at the center of the tumor mass which do have access to normal blood vessels [15].
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4.2. The types of tumor

4.2.1. On the basis of the type of cell initially altered

Tumors are named depending upon the type of cell from which they originate. These include:
• Carcinomas, which result from altered epithelial cells. They constitute the highest ratio in all types of cancer.

• Sarcomas denote the cancer abnormalities in the bone, muscle, fats, and connective tissue.

• Leukemia, which originate from cancerous white blood cells.

• Lymphoma, which is a malignancy of the lymphatic system or cells which are derived from the bone marrow
(BM).

• Myelomas depict the cancers of those particular white blood cells that synthesize antibodies.

4.2.2. Classification by grade

This is the abnormality in cells with respect to their surrounding normal tissues. Increase in abnormality increases
the grade, from 1 to 4. Well-differentiated cells closely resemble normal cells and belong to low-grade tumors.
Improperly differentiated cells are highly abnormal with respect to the surrounding tissues[16]. These are high-
grade tumors.

Grade 1: This includes well-differentiated cells having slight abnormality.

Grade 2: These cells are moderately differentiated and a bit more abnormal.

Grade 3: The cells are improperly differentiated and very abnormal in context of having mutated chromosomes
and produce some harmful chemicals which affect nearby cells and may enter in the blood.

Grade 4: Cells are immature, primitive, and undifferentiated.

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
5. Causes of cancer
Origin and advancement of cancer depend on many factors inside the cell (mutations, immune conditions, and
hormones) as well as external factors from the environment (smoking, chemicals, infectious organism, and
radiations). These entire elements act together to cause abnormal cell behavior and uncontrolled proliferation.
The resultant unusual cell mass in the body grows and affects normal tissues in their surroundings, and
sometimes it also spreads to the other localities in the body (metastasis)[17] (Figure 1). According to the most
accepted model for cancer causation, mutations in tumor suppressor and oncogenes is the major factor leading
to the cancer development. Another model suggests that some mutation in a master gene that control the
division of cells can also shepherd normal

Figure 1. Factors involved in causing cancer

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
 cells toward abnormal chromosomal replication, which can result in duplication or deletion of the entire
sections of chromosomes[18]. This change in genetic content in the cells produces abnormal amount of
a specific protein irrespective of the actual need. If any chromosomal aberration affects a protein that
plays a crucial role in cell cycle, quantitatively or qualitatively, it may result in cancer. There is also a
strong indication that the unnecessary addition (hypermethylation) or deletion (hypomethylation) of
methyl groups to genes involved in the regulation of cell cycle, DNA repair, and apoptosis is also
associated with some cancers. It is necessary to commemorate that cancers can take months to years for
accretion of DNA mutations enough for the resultant cancer mass to be detectable. Thus, there can be
several mechanisms which lead to the development of cancer. This further obscures the difficult task of
defining the actual cause of cancer[19].

5.1. Mutations in the p53 tumor suppressor gene Considering biochemical pathways the most important
component central to human carcinogenesis is the P53 gene whose normal function is associated with
gene transcription, DNA synthesis, apoptosis, and DNA repair[20]. Alterations and mutations in p53 elicit
the development of primary tumors. The biochemical processes related to the normal function of p5 gene
are performed by multiunit protein machines. The functions of these machines are altered by some viral
oncoproteins, which bind with the p53 and perturb its interactions with other cellular protein
components[21].

5.2. Linking tumor viruses to human cancer Development of human malignancies is strongly associated
with viruses. In fact, 15% of the cancer are believed to be caused by oncogenic viruses which include
human papillomaviruses (HPVs), Epstein–Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus
(KSHV, also known as HHV-8), and hepatitis B and C virus (HBV and HCV)[22]. Another virus known
as Merkel cell polyomavirus (MCPyV) has been recently described causing Merkel cell carcinoma, a rare
but aggressive type of skin cancer[23]. The recent studies on these cancer-causing agents have been very
helpful to understand the basic biology of cell and how disturbances in the cellular pathways lead to the
initiation and maintenance of cancer.

KCT’S R. G. Sapkal College of Pharmacy, Nashik 7

6. Cancer treatment modalities

Since the recognition of the malignancy, the objective of extraordinary research is to discover novel
methods of quality treatment approaches for cancer. Presently, over 60% of all ongoing medical quality
treatment trials worldwide are concentrating on cancer[24]. The selection of treatment and its progress
depends on the type of cancer, its locality, and stage of progression. Surgery, radiation-based surgical
knives, chemotherapy, and radiotherapy are some of the traditional and most widely used treatment
methods. Some of the modern modalities include hormone-based therapy, anti-angiogenic modalities,
stem cell therapies, immunotherapy, and dendritic cell-based immunotherapy. Side effects associated with
traditional methods of cancer treatment highlights the scope of novel cancer treatment methods. Different
novel treatment systems utilized for the treatment of malignancy include treatment against angiogenic
ability of cancers, oncolytic virotherapy, hereditary control of apoptotic and tumor-attacking pathways,
antisense, and RNAi techniques. These treatments are employed against the cancer of the cerebrum,
prostate, lung, breast, colorectal, pancreatic, liver, head and neck, bladder, skin, ovarian, and renal
malignancy[25]. The coming sections of the chapter will shed light on the abovementioned treatment
modalities.

6.1. Surgical removal of tumors

Surgery, resection, or operation is thought as one of the most promising and conventional treatments of
many benign and malignant tumors as it assures least damage to the surrounding tissues as compared to
chemotherapy and radiotherapy. Another reason of considering surgery as the preferred treatment option
is that the tumor can be removed without unnecessary risk of tissue damage. Different kinds of surgeries
either open or minimally invasive can be performed depending upon various factors:

• The reason of the surgery

• The part of the body where surgery is to be performed

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
• The mass of tumor to be removed • Patient’s preference Surgeries also vary depending upon the stage of
cancer. Surgery may:

• Remove the entire tumor from a certain part

• Debulk a tumor in case its removal may cause damage to a certain organ

• Ease cancer symptoms in cases when a large tumor is causing pain or intense pressure on any body part

In case of open surgery, one large cut is made, and it usually results in removal of the tumor along with
some amount of healthy tissues associated with some closely present lymph nodes. In contrast, for
minimally invasive surgery, the surgeon makes a few small cuts instead of one large one and then with the
aid of laparoscope which is a thin tube with a camera attached to it views the tumor in detail. The camera
shows the image on a screen which helps the surgeon to monitor his activity [26]. The tumor, along with
small amount of healthy tissues, is then carefully removed with the assistance of specialized surgery tools

6.2. Radiation-based surgical knife

6.2.1. Stereotactic radiosurgery (SRS)

Stereotactic radiosurgery (SRS) is a kind of therapeutic radiology in which ionizing radiations are used for
the damage and destruction of selected areas within an organ or tissue. This technique exposes a small
area of the body to a very high dose of radiations. However, no cutting or blade is used in the entire
process, but it is still called a surgery because the results of this treatment are quite similarly an ordinary
surgery [27]. As the beam of radiations administered is of very high dose, it is very important that the
beam of radiation is highly focused so that the peripheral tissues are left unaffected. It is primarily utilized
in cases of brain tumors at locations where conventional surgical techniques are hard or unsafe to use or in
other cases when the health status of a patient does not support him to tolerate a surgical procedure [28].

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
6.2.2. Gamma knife systems

A Gamma Knife technique does not include real surgery, nor is the Gamma Knife actually a blade. It
utilizes light emissions, centered gamma beams to treat little to medium-sized sores and tumors. Many
radiation beams combine to concentrate on the cell mass under treatment, giving an exceptionally high
dose of radiation without a surgical cut or opening [29].

6.2.3. Linear accelerator (LINAC) systems

Linear accelerator (LINAC) systems utilize high-energy X-rays to treat a tumor or other injuries. Some
basic kinds of LINAC frameworks include CyberKnife®, X-Knife®, Novalis®, and Peacock®. LINAC
frameworks can treat bigger tumors and bigger affected regions than the Gamma Knife. Zones other than
the brain can be treated with a LINAC framework [30].

6.2.4. Proton beam therapy or cyclotron

Proton beam therapy is a sort of molecular radiation treatment. As opposed to utilizing beams of radiation,
for example, gamma beams or X-beams, molecular radiation treatment utilizes particles, like protons or
neutrons[31].

6.3. Radiation therapy

The discovery of X-rays by German physicist Wilhelm Conrad Rontgen in 1895 also marked their clinical
importance in the treatment of cancer. After that, almost a hundred years ago, Marie Curie’s research in
radium makes her a two-time Noble Prize winner and the one to introduce the field of radiotherapy in
medicine. The 2011 thus became the Year of Radiation Therapy, announced by the UK, enclosing a
century of developments in radiation therapy. Radiation therapy, now a distinguished field of
specialization in medicine with branches such as that of radiation oncology, employs professionals from
various sectors of health sciences working on the field’s advancements [32].
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6.3.1. Principles of radiation therapy

Radiation in cancer therapy can be described as a physical entity used to kill the cancer cells. The kind of
radiation used in therapy is ionizing radiation. The radiation upon incidence causes particles in biological
bodies to charge electrically; thus, the term is “ionizing,” and energy is transferred in this way from the
rays to the cells of the body through which it passes. This energy can either directly kill cancer cells or
genetically alter them so that they accede to apoptosis and cell death.

The mechanism underlying genetic alterations in cells treated with radiation lies in the fact that the
damaged DNA is unable to replicate and thus cell division is halted, which in turn causes cells to die. The
adverse effect of radiation therapy is that it also hits normal cells lying in the peripheries of the main
tumorous mass. However, improved imaging techniques and attempts at accurate targeting of the cancer
mass in addition to the normal cells’ ability to regain normal function faster than cancer cells as cancer
cells lack efficient repair systems minimize the net damage done by radiation [33].

6.3.2. Radiation therapy techniques

6.3.2.1. Fractionation Fractionated delivery of radiation therapy employs the radiobiological difference of
normal and cancer cells, multiplying the survival edge of normal cells over cancer cells, by many folds,
since they have an intact repair system triggered by sublethal dosages of radiation.

6.3.2.2. 3D conformal radiotherapy (3DCRT)

The usage of 2D rectangular fields in therapy has become obsolete, making CT scan-based 3D radiation
therapy the primary method for detection of cancer masses, avoidance of vital organs, and target selection
for radiation therapy [34].

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
6.3.2.3. Intensity-modulated radiation therapy (IMRT)

This technology uses an inverse planning software, which modulates the intensity of radiation beams used
during therapy, resulting in an irregularity of radiation dosages that differentially target tumor as opposed
to vital organs [35].

6.3.2.4. Image-guided radiotherapy (IGRT)

Using imaging techniques prior to therapy, such as IGRT, helps position radiation correctly, diverting rays
away from critical organs, targeting only tumor masses, and consequently reducing organ damage as a
result of errors in aiming (Figure 2)[36].

6.4. Chemotherapy

Chemotherapy halts tumor progression by killing off their ability to divide and enforcing apoptosis.
Normal biological functioning of the body refreshes cells of the body by removing excess cells or
damaged cells and thus signaling new cell formation. In contrast, tumor cells have an increased capacity to
divide and the quality of immortality as they are not controlled by apoptosis. Therefore, where in normal
bodies the cell proliferation is balanced by cell death and is regulated, in cancerous masses, cell
proliferation to cell death ratio is high. Chemotherapy acts here to bring about changes in the tumor cells
so that they stop growing or die; thus, the two branches of chemotherapeutic drugs are cytostatic
(biological drugs) and cytotoxic, respectively However, chemotherapeutic drugs also target normal cells,
which could result in a variety of side effects depending on the dosage such as hair loss, nausea, fatigue,
vomiting, etc. As a result of vigorous chemotherapy treatment, patients become immunocompromised;
this can result in complicated infections and consequently death. Out of chemotherapeutic drugs
discovered, a total of 132 are FDA approved. These drugs are designed to specifically target[37].

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
The use of chemotherapy as a treatment for cancer started in the beginning of the twentieth century.
Effects of drugs studied in four programs conducted in World War II were the leverage over which a
national effort to develop drugs was initiated in 1955, known as Cancer Chemotherapy National Service
Center. Two diseases, acute childhood leukemia and advanced Hodgkin’s disease cured using
combination chemotherapy in the 1960s and 1970s, respectively, lead to acceptance of the ability of drugs
to cure complicated cancers. This also encouraged studies on adjuvant chemotherapy by the aid of
national cancer program. Molecular studies on abnormalities in cancer cells are an important screening
process today for checking the effectiveness of new drugs and designing targeted therapies. This has
advanced chemotherapy today.

Drugs used in chemotherapy are now known to be more than a 100 in number which can be used alone or
in combination therapies. Each drug has a different chemical structure and composition. While surgery
and radiation are invasive and targeted procedures, chemotherapy is mainly systemic, traveling through
the body to reach cancer cells[38].

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
6.4.1. Different types of chemotherapy drugs

Mode of action, chemical structure, composition, and homology to other drugs are factors that help
categorize chemotherapy drugs. Some drugs may fall into more than one category as they may have
multiple modes of action. To know the side effects of a particular drug, one must study the mode of
action. This information can later be incorporated by oncologists to predict how effective a drug will
work. In combination chemotherapies, drug studies help decide the time, order, and dosages of each drug
administered in the therapy[39].

6.4.1.1. Alkylating agents

Direct DNA damage by alkylating agents stops division of cancer cells and is efficacious in all stages of
the cell cycle. Many cancers are treated with alkylating agents such as lymphoma, leukemia, multiple
myeloma, Hodgkin’s disease, and sarcomas [40]. Also included are several cancers of the ovary, breast,
and lungs. On the downside of alkylating agents, they can cause damage to bone marrow as they damage
DNA. Long-term damage can result in acute leukemia, depending on dosages used, although rarely.
Leukemia from alkylating agents arises after 5 to 10 years of treatment. Families of alkylating agents are
given in Table 1.

Based on similar mode of action of alkylating agents and platinum drugs, i.e., cisplatin, carboplatin, and
oxaliplatin, they are sometimes grouped together. These drugs have a reduced tendency to cause
posttreatment leukemia
6.4.1.2. Antimetabolites

These drugs are analogs for the units of DNA and RNA, and hence by incorporation, they stop growth of
DNA and RNA. Such drugs particularly effect the S phase of the cell and used for 148 Neoplasm the
treatment of leukemia, cancers of ovary, breast, intestinal tract, and various others. Examples of
antimetabolites are given in Table 1.

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
6.4.1.3. Anthracyclines
These are antibiotics in nature which target DNA replication enzymes, effecting cells in all phases of the
cell cycle. Various cancers lie in the scope of these drug treatments. A big limitation of these drugs is that
exceeding a critical limit can permanently damage the heart. Therefore, dose limits for a lifetime are
determined for these drugs. Classes of anthracyclines are mentioned in Table 1.

6.4.1.4. Other antitumor antibiotics

There are some antitumor antibiotics that do not belong to anthracyclines, including actinomycin D+,
bleomycin, and mitomycin C. Another anticancerous antibiotic is mitoxantrone, comparable in many ways
to doxorubicin, both of which can damage the heart at high dosage. Their mode of action is also the same,
i.e., inhibiting the topoisomerase II, and thus can lead to posttreatment acute myelogenous leukemia, after
2–3 years in most cases. Prostate and breast cancers, lymphoma, and leukemia are also treated with
mitoxantrone.
6.4.1.5. Topoisomerase inhibitors
Topoisomerase inhibitors deter the unwinding of DNA and hence stop DNA replication. Some leukemia;
ovarian, gastrointestinal, and lung cancers; and others are treated with these drugs. Examples of
topoisomerase I inhibitors are topotecan and irinotecan (CPT-11), and examples of topoisomerase II
inhibitors are etoposide (VP-16) and teniposide. Mitoxantrone also constrains topoisomerase II.

6.4.1.6. Mitotic inhibitors

Mitotic inhibitors are plant alkaloids and other naturally derived products in nature. They inhibit synthesis
of proteins necessary for cell division, particularly in the mitotic phase of the cell cycle, subsequently
damaging all other phases too. Cancers treated with these drugs include lung, breast, myelomas, leukemia,
and lymphoma. Side effects such as peripheral nerve damage can put limits to dosages of these drugs.
Examples of mitotic inhibitors are given in Table 1.

6.4.1.7. Miscellaneous chemotherapy drugs

Some uncategorized chemo drugs with uncommon modes of action include the enzyme Lasparaginase and
an inhibitor of proteasome called bortezomib (Velcade®). Examples include drugs like L-asparaginase; it
is an enzyme, and the proteasome inhibitor is bortezomib (Velcade®)[41].
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6.5. Hormone therapy
Advancements in the field of molecular biology in recent years clarified the role of hormones in cell
growth and in the regulation of malignant cells. Nearly 25% of tumors in men and 40% in women are
known to have hormonal basis[42]. Hormonal treatment is effective to treat cancer without any
cytotoxicity which is associated with chemotherapy. Steroids are hormone in nature, and such hormone-
like drugs are used in treatment of cancers like lymphoma, leukemias, and multiple myeloma[43].
Moreover, corticosteroids are used as antiemetics, which give relief from nausea and vomiting after
chemotherapy. Also used before chemotherapy, they mitigate hypersensitivity to the treatment. Only when
used in actual chemotherapy procedure, these drugs are called as chemotherapeutic drugs[44].

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DCs are derived from bone marrow progenitors and circulate in the blood as immature precursors prior to
migration into peripheral tissues. Within different tissues, DCs differentiate and become active in the
taking-up and processing of the antigen[46]. The location of the DCs inside the body is unique to capture
the foreign antigens such as body surfaces like the skin, pharynx, upper esophagus, vagina, ectocervix,
and anus and at mucosal surfaces, such as the respiratory and gastrointestinal systems . In steady-state
conditions, in most tissues DCs are immature, unable to stimulate the T cells due to the lack of required
accessory signals such as CD40, CD54, and CD86, but they are highly equipped with the antigen-
capturing Fcγ and Fcε receptors to uptake the antigens[47] . Upon antigen uptake and appropriate
stimulation, DCs undergo further maturation and migrate to secondary lymphoid tissues where they
present Ag to T cells and induce an immune response.
Inaba et al. (1990) first described the role of DCs as adjuvants. In this study, DCs isolated from mouse
spleen were primed with the specific antigen overnight. DCs processed and presented the antigen epitopes
onto MHC molecules, and Ag-loaded DCs were then injected into mice, which led to Ag-specific T-cell
sensitization and development of immunity. The immune response was robust when the mouse was
challenged again with the DC pulsed with the same antigen, due to the presence of memory cells [48].

Methods of preparing DCs have changed since they were considered trace cell types of the immune
system, when in vitro protocols were employed to grow DCs from their progenitors. Inaba et al. identified
and reported clusters of DCs from cultures of mouse blood supplemented with GM-CSF . Bone-marrow
being the precursor of DCs, they were soon thereafter identified in the blood culture, and a method was
thus described to grow large numbers of DCs from bone marrow (BM) cultures of mice supplemented
with GM-CSF. These new methods of DC culture paved the way to further characterize DCs and
investigate their clinical application. In order to investigate the capacity of BM-derived DC (BMDC) to be
used as an adjuvant to induce immunity against infectious diseases, BMDCs were pulsed with bacillus
Calmette-Guerin organism and induced a strong T-cell response when injected in vivo.

To investigate the role of DCs as adjuvant in humans, they are prepared from the culture of blood
monocytes supplemented with GM-CSF and IL-4[49]. Later, a method to generate mature DCs from
human blood was described in which they used macrophage-conditioned media containing essential
maturation factors . DCs generated with this method were clinically more potent as an adjuvant.

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
Briefly, to produce autologous dendritic cell vaccines for cancer immunotherapy, monocytes are harvested
from cancer patients by leukapheresis and cultured in the presence of GM-CSF and IL-4 supplements to
generate monocyte-derived DCs. These immature monocyte-derived DCs can subsequently be loaded with
tumor-derived antigens using different methods. Firstly, DC can be fed with the autologous tumor lysate
prepared from the tumor biopsy of the concerned patients. Secondly, DC can be electroporated with
tumor-derived mRNA. However, if the access of autologous tumor is too limiting, then DCs may be
loaded with allogeneic tumor proteins or common tumor-associated antigens (TAAs). DCs loaded with the
relevant tumor peptides/antigens are activated using Toll-like receptor ligands or activating cytokines. The
mature DCs loaded with tumor antigens are then stored and transported in dry ice to be.

Figure 3. Schematic presentation of autologous dendritic cell vaccine preparation for cancer
immunotherapy

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
used as autologous DC-based cancer vaccine as shown in Figure 3. When injected into cancer patients,
tumor antigen loaded DCs are drained into the local lymph nodes and induce tumorspecific T-cell
immunity which helps to fight against the cancer cells of the patient[50].

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KCT’S R. G. Sapkal College of Pharmacy, Nashik
7. Conclusion

Cancer is one of those diseases that are emerging very rapidly throughout the world, and it is affecting
about 82% of the world’s population. Cancer is a complex disorder involving complex alterations in the
physiological conditions of the body. Considering its severe complications, there is a crucial need to
search active treatment modalities for cancer. Some of the traditional methods like radiotherapy,
chemotherapy, and surgery are still considered effective, but due to certain side effects to the normal body
cells, we owe to work for some advancement in cancer treatment modalities. In recent times hormone-
based therapy, gene therapy, stem cell

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8. References
[1] Ferlay J et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International
Journal of Cancer. 2010;127(12):2893-2917

[2] Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011;144(5): 646-674

[3] Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metabolism.
2016;23(1):27-47

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