Gene Therapy In The Treatment Of Cancer

1. KENDRIYA VIDYALAYA TAMULPUR
BIOLOGY INVESTIGATORY PROJECT REPORT
TOPIC : - GENE THERAPY IN THE
TREATMENT OF CANCER
2017-18
PREPARED BY:-
NAME: PUJA DAS
ROLL NO : 3626242
CLASS: XII
GUIDED BY : MISS BILKIS BARBHUIYAN, (PGT , BIOLOGY)

2. CERTIFICATE
This is to certify that Puja Das of
Class- XII carried out the work entitled ‘GENE
THERAPY IN THE
TREATMENT OF CANCER ’ under
my supervision for the session 2017-18.
This work is a part of Biology practical 2017-18.
The project report is the result of his original work
and therefore recommended for submission for the
fulfillment of the Biology Practical.
Signature Signature Signature
[Sub. Teacher] [Ext. examiner] [Principal]

3. ACKNOWLEDGEMENT
At the very outset I express my
thankfulness to respected Bilkis Barbhuiyan,
PGT Biology, KV Tamulpur, for her guidance
during the preparation of the project report
on every step.
I am also grateful to Mr. Gurupad Talukdar
, Principal, KV Tamulpur, Baksa to give me the
permission to study such concern topic.
DATE: PUJA DAS
PLACE : Class: XII
Tamulpur KV Tamulpur
Baksa

4. CONTENTS
1.ABSTRACT
2.INTRODUCTION TO GENE THERAPY
3.A SMALL OVERVIEW OF CANCER
4. RELATION BETWEEN GENE AND CANCER
5.CURE OF CANCER WITH GENE THERAPY
6. CURRENT APPROACH TO GENE THERAPY
7. ONGOING RESEARChES TO CURE CANCER
WITH GENE THERAPY
8. RECENT REPORT ON GENE TRANSFER
CLINICAL TRIALS
9. POSITIVE AND NEGATIVE EFFECTS OF
GENE THERAPY
10. CONCLUSION
11. REFERENCES

5. ABSTRACT
This is a small investigatory
project to focus on a major issue
of today’s world- ”Gene Therapy
In The Treatment Of Cancer”. In
this project , I have tried to
highlight on two main things,
gene therapy and cancer .And the
relation between both. So that
the further researches could be
done to find a better solution to
cure a deadly disease like cancer.

6. INTRODUCTION TO GENE THERAPY
Gene therapy
Gene therapy is a collection of method that
allows correction of gene defects,
diagnosed in a child or an embryo.
1. In gene therapy, genes are inserted into a
person’s cells and tissues to treat a
disease.
2. Correction of a genetic defect involves
delivery of a normal gene into the
individual or embryo to take over the
function or to compensate for the non
functional gene.
3. First gene therapy was given to a four
year old girl with Adenosine Deaminase
deficiency by M Blease and WF Andresco in
1990s.
So to say in simple words,Gene therapy is a
type of treatment which uses genes to
treat illnesses

8. A small overview of cancer
Cancer is one of the most dreaded diseases in human
beings. Cancer is a group of diseases involving
abnormal cell growth with the potential to invade or
spread to other parts of the body. These contrast with
benign tumors, which do not spread to other parts of
the body. Possible signs and symptoms include a
lump, abnormal bleeding, prolonged cough,
unexplained weight loss, and a change in bowel
movements. While these symptoms may indicate
cancer, they may have other causes. Over 100 types of
cancers affect humans.
Tobacco use is the cause of about 22% of cancer
deaths. Another 10% are due to obesity, poor diet,
lack of physical activity, and excessive drinking of
alcohol. Other factors include certain infections,
exposure to ionizing radiation and environmental
pollutants. In the developing world nearly 20% of
cancers are due to infections such as hepatitis B,
hepatitis C and human papillomavirus infection.
These factors act, at least partly, by changing the
genes of a cell. Typically many genetic changes are
required before cancer develops. Approximately 5–
10% of cancers are due to inherited genetic defects
from a person's parents. Cancer can be detected by
certain signs and symptoms or screening tests. It is
then typically further investigated by medical
imaging and confirmed by biopsy.

11. RELATION BETWEEN GENE AND CANCER
All cancers are caused by changes to materials in our bodies
called “genes.” When genes are damaged, they can develop
changes called “mutations.” Over time, damage can accumMulate
in cells, causing them to grow out of control And cause cancer.
It takes more than one gene mutation for cancer to occur. For
most people who develop cancer, the cancer-causing gene
mutations happen over the course of a lifetime, leading to cancer
later in life. Some people are born with a gene mutation that they
inherited from their mother or father. This damaged gene puts
them at higher risk for cancer than most people. When cancer
occurs because of an inherited gene mutation, it is referred to as
hereditary cancer. Cancers that are not due to an inherited gene
change are called “sporadic cancer.”
DETAILED EXPLANATION
In order to understand the genetic mechanisms of how genes
cause cancer, it is important to review some basic genetic
concepts. Genes come in pairs, and work together to make a
protein product. One member of the gene pair comes from the
mother, while the other member is inherited from the father.
Eggs and sperm are called "germ cells." When an alteration or
mutation in a gene is present in the germ cells, it is referred to as
a "germline mutation." When a germline mutation is inherited, it
is present in all body cells. On the other hand, mutations that we
are not born with, but that occur by chance over time in cells of
the body are said to be "acquired." Acquired mutations are not
present in all cells of the body, are not inherited, and are not
passed down to our children. Acquired mutations are always
involved in causing cancer. Germline mutations are involved in a
small percentage of cases.

12. The formation of tumors basically results from cell growth that
gets out of control. In the human genome, there are many
different types of genes that control cell growth in a very
systematic, precise way. When these genes have an error in their
DNA code, they may not work properly, and are said to be
"altered" or mutated. An accumulation of many mutations in
different genes occurring in a specific group of cells over time is
required to cause malignancy. The different types of genes, that
when mutated, can lead to the development of cancer are
described below. Remember, it takes mutations in several of
these genes for a person to develop cancer. What specifically
causes mutations to occur in these genes is largely unknown.
However, mutations can be caused by carcinogens
(environmental factors known to increase the risk of cancer).

13. CURE OF CANCER WITH GENE THERAPY
Gene-based therapies for cancer in clinical trials include strategies that involve
augmentation of immunotherapeutic and chemotherapeutic approaches. These
strategies include ex vivo and in vivo cytokine gene transfer, drug sensitization with
genes for prodrug delivery, and the use of drug-resistance genes for bone marrow
protection from high-dose chemotherapy. Inactivation of oncogene expression and
gene replacement for tumor suppressor genes are among the strategies for targeting
the underlying genetic lesions in the cancer cell. A review of clinical trial results to date,
primarily in patients with very advanced cancers refractory to conventional treatments,
indicates that these treatments can mediate tumor regression with acceptably low
toxicity. Vector development remains a critical area for future research. Important
areas for future research include modifying viral vectors to reduce toxicity and
immunogenicity, increasing the transduction efficiency of nonviral vectors, enhancing
vector targeting and specificity, regulating gene expression, and identifying synergies
between gene-based agents and other cancer therapeutics.
The evolution of gene therapy has taken a somewhat unexpected course on the basis of
these rather conceptually simple beginnings. Most of the approved protocols for what is
now called gene therapy involve cancer patients. This would not have been anticipated
because cancer seems to be a particularly unsuitable target for the classical approach
of gene-replacement therapy. Cancer generally arises as the culmination of a multistep
process that involves a variety of somatic gene alterations. At first blush, it might
appear necessary to be able to correct all of the genetic abnormalities in the cancer
cell, which is daunting since all of these are not known. It would also seem necessary to
restore normal gene function to every cancer cell, which is beyond the capabilities of
the vectors currently available for use in gene therapy. As it turns out, these
considerations may not limit strategies involving gene replacement for therapy of
cancer (more on this below). For these reasons, cancer gene therapy has focused
instead on using recombinant DNA constructs to augment existing therapies. The
treatment strategies that have evolved include the use of recombinant vaccines as
immunotherapeutics, the protection of bone marrow during chemotherapy by
transducing a drug-resistance gene into marrow stem cells, and the use of expression
vector constructs that bring about the conversion of inactive prodrugs into active
drugs. Some individuals may contend that these interventions do not constitute gene
therapy but that they are instead recombinant DNA therapeutics that do nothing to
restore normal functioning genes to the cancer cell. There is some merit in this
distinction, since in some instances, the genes being introduced into the cells have no
direct therapeutic function. Certainly, in situations where the introduced DNA is for
diagnosis or prevention, the term therapy should not be used ( 8 ). On the basis of this
classification, many of the interventions to date in cancer would be classified as gene
therapeutics as distinct from gene-replacement therapy.

14. CURRENT APPROACH TO GENE THERAPY
Now a days many types of gene replacement therapies are carried
out to cure cancer. Some are as follows:
Immunotherapy Using Recombinant DNA Constructs Expressing
Cytokines and Lymphokines
1.Drug-Sensitivity Genes
Selective transduction of tumor cells with a gene whose product can
convert a relatively nontoxic prodrug administered systemically to a
toxic metabolite in the cancer cell was one of the first strategies
proposed for the use of recombinant DNA constructs in cancer
patients. In the first protocol to be approved using this strategy,
brain tumors are transfected with a retroviral vector expressing the
herpes simplex virus thymidine kinase (HSV-TK) gene. Systemic
gancyclovir that enters the tumor cell is metabolized to cytotoxic
gancyclovir triphosphates by cells expressing HSV-TK ( 30 ). A
potential advantage of this technique is selective uptake of the
vector and expression by proliferating cells, presumably the tumor
cells. Studies ( 31 – 33 ) in a rat glioma model showed that marked
tumor regression occurred when only a small fraction of tumor cells
were transfected with the retroviral HSV-TK. This cytotoxic effect of
transduced on nontransduced cells has been termed the “bystander
effect.”
2.Drug-Resistance Genes
The transfer of genes into normal cells to augment existing cancer
treatments is also under investigation. Current protocols are
attempting to enhance marrow protection during chemotherapy by
transducing the multiple-drug resistance gene (MDR1) into normal
bone marrow or blood-derived stem cells ( 36 , 37 ). The MDR1 gene
produces P-glycoprotein, which functions as a cellular efflux pump
and may be responsible for the resistance of some tumor cells to
various hydrophobic cytotoxic drugs. Insertion of the MDR1 gene
into normal marrow stem cells produces a population of cells that
can be selected for resistance to a systemically administered

15. chemotherapeutic agent ( 38 , 39 ). A potential advantage of this
approach is that it may permit higher doses of chemotherapy to be
given with less toxicity and more efficacy
3.Tumor Suppressor Gene Replacement and
Oncogene Inactivation
The identification of specific genes that contribute to the
development of cancer presents an opportunity to use these genes
and their products as prevention and treatment targets. The genes
that are implicated in carcinogenesis include dominant oncogenes
and tumor suppressor genes ( 43 , 44 ). Proto oncogenes (normal
homologues of oncogenes) participate in critical cell functions,
including signal transduction and transcription, but only a single
mutant allele is required for the malignant transformation of a cell.
Primary modifications in the dominant oncogenes that confer gain of
transforming function include point mutations, amplifications,
translocations, and rearrangements. Tumor suppressor genes,
which regulate gene transcription and cell proliferation, undergo
homozygous loss of function, either by mutation, deletion, or a
combination of these. It is possible that modification of the
expression of dominant and tumor suppressor oncogenes may
influence certain characteristics of cells that contribute to the
malignant phenotype. Thus, gene replacement could mediate
induction of tumor cell death by direct killing (e.g., apoptosis) or a
bystander effect, induction of tumor cell dormancy, or prevention of
malignant progression of premalignant cells.
4.Tumor suppressor genes
The inactivation of certain genes may contribute to tumor growth. In
one scenario, both copies of the gene must be eliminated or
inactivated to eradicate the growth-suppressive function of the gene
( 43 , 56 , 57 ). Theoretically then, replacement of a functioning copy
of the tumor suppressor gene in cells with homozygous loss of
function could restore normal growth and proliferation pathways.

16. ONGOIN RESEARCHES to cure cancer with
gene therapy
Some of the latest news which proves about the ongoing
researches on gene therapy are as follows:
1.CAR T Cells: Engineering Patients’ Immune Cells
to Treat Their Cancers
Updated: December 14, 2017
Co-stimulatory signaling domains have been added to newer generations of CAR
T cells to improve their ability to produce more T cells after infusion and survive
longer in the circulation.
Credit: Brentjens R, et al. “Driving CAR T cells forward.” Nat Rev Clin Oncol.
2016 13, 370–383.

17. 2. Study Identifies Potential Cause of
Hearing Loss from Cisplatin
January 26, 2018, by NCI Staff
The chemotherapy drug cisplatin (in green) in a mouse inner ear.
The drug was found to be retained in the inner ears of both mice and
humans months or even years after treatment.
Credit: National Institute on Deafness and other Communication
Disorders
When I visited the site of NCI to know about
some other researches I got the results as
follows :
NCI Search Results
Results for: ongoin researches to cure cancer with gene therapy
Results 1–10 of 17377 for: ongoin researches to cure cancer with gene therapy

18.  Gene Therapy in Mouse Model of Ovarian Cancer
A gene therapy approach blocked tumor growth in mice with ovarian cancer.
https://www.cancer.gov/news-events/cancer-currents-
blog/2015/genetherapy-ovarian
 Nanotechnology Cancer Therapy and Treatment
Nanotechnology offers the means to target therapies directly and selectively
to cancerous cells and neoplasms. With these tools, clinicians can safely and
effectively deliver chemotherapy, radiotherapy, and the next generation of
immuno- and gene therapi
https://www.cancer.gov/sites/ocnr/cancer-nanotechnology/treatment
 CURE Honors
In celebration of 21 years of the CURE program, CRCHD honors
outstanding CURE scholars, mentors, and champions.
https://www.cancer.gov/about-nci/organization/crchd/diversity-
training/cure/honors
 Targeted Therapy for Cancer
Targeted therapy is a type of cancer treatment that targets the changes in
cancer cells that help them grow, divide, and spread. Learn how targeted
therapy works against cancer and about side effects that may occur.
https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies

19. RECENT REPORT ON GENE TRNSFER CLINICAL TRILS
Cancer
Transferred
genes
ClinicalTrials.gov47
identifier #
Description Phase
Pancreatic Rexin-G NCT00121745 A cytocidal cyclin G1
construct accumulates
preferentially in the
tumor cells to block the
action of cyclin G1 and
initiate cell death
I
Glioblastoma HSVtk NCT00001328 The HSVtk gene is
introduced into
glioblastoma cells via a
mouse retrovirus.
Glioblastoma cells with
the HSVtk gene are
then sensitive to the
drug glanciclovir which
is administered
I
Head and
neck
p53 NCT00041613 Transfer of the p53
gene via a replication
incompetent
adenovirus to tumor
cells to inhibit cell
growth and induce
apoptosis
III
Melanoma MDA-7 NCT00116363 MDA-7 a novel tumor
suppressor molecule is
introduced into the
melanoma cells and
overexpression inhibits
cellular proliferation
and induces apoptosis
II
Pancreatic TNF-α NCT00051467 The TNF-α gene under
the control of a
radiation inducible
promoter is introduced
into tumor cells and in
combination with the
radiation therapy
induces cell death
II

20. POSITIVE AND NEGATIVE EFFECTS OF
GENE THERAPY
Positives and Negatives
Positives Negatives
 1. Many countries have been approved
for trials in human gene therapy including
USA, China, France, Italy, and the
Netherlands
 2. The public’s opinion impacts the
influence on whether the trials get approved
or not
 3. 52% of the USA said it was acceptable
to perform gene therapy
 It can wipe out genetic disease before
they can begin and reduce suffering for
future generations
 4. Gene therapy is a 'medicine" for the
future since it can control or get rid of
hereditary diseases
 5. People suffering from genetic disorders
like Parkinson's disease, Alzheimer's disease
and Huntington's disease are some of those
whose only hope for cure is gene therapy.
 1. Some people think we will have to pay
the price trying to play “God”
 2. gene therapy may be used for the
enhancement or change of human
capabilities
 3. this form of treatment be a luxury only
for the rich which could very well make the
rich, richer and make the poor, poorer
 4. All gene therapy experiments must
receive approval from the Recombinant DNA
Advisory Committee (RAC) and the National
Institutes of Health (NIH). After approval by
these committees the trials must also
receive approval from the U.S. Food and
Drug Administration (National Cancer
Institute,1993)
 5. 74% of the Japanese thought that gene
therapy was unacceptable
 6. 42% of the USA said that changing
genetic makeup was wrong
 7. In Japan and New Zealand, 63 % of the
people suggested that gene therapy was a
form of playing God.
 8. Gene therapy could possibly be only for
the rich and not the poor
 9. Gene therapy will be used to create a
superior race
 no guarantee that the viral enzyme 
responsible for this step will be able to
introduce the correct gene at the specific
point in the host chromosome
 10. Error in the genetic makeup of the cell

21. and can result in serious disorders.

22. CONCLUSION
From the above report, I have come into a conclusion that
although gene therapy is very beneficial in curing cancer but
most part of the society cannot effort it. Also gene therapy
has many side effects which are also to be kept in mind to
avoid any kind of injury.
Currently, the success of cancer gene therapy is lagging
behind that obtained in the treatment of monogenetic
diseases. Although cancer is a genetic disorder, the
abnormalities are generally polygenic and genetic variation
between individuals or even tumors at different sites within
the same patient are substantial. The major reasons for
failure or limited success of cancer gene therapy are not only
technical, which we have discussed in this review, but also
related to ethical, policy and financial issues. The fear of
insertional mutagenesis also raises further health risk
concerns. The possibility of passing the genetic changes onto
offspring is an argument used against human cancer gene
therapy involving approaches that result in integration into
the genome. Unlike chemotherapies, gene therapies are only
effective in a subset of patients with any given cancer,
making each gene therapy agent an orphan drug. Moreover,
failure to target metastatic cells, the major driver of cancer-
associated mortality has limited the general utility of cancer
gene therapy. Targeting of metastases using gene therapy
approaches has proven inefficient for many reasons
including genetic and epigenetic heterogeneity, development
of resistance and difficulty in locating metastases, which
can frequently be disseminated throughout the body.
Ideally, gene therapy should provide a means of treating
primary and disseminated tumors, with a minimal effect on
normal cells. This problem can be resolved by using a gene
product with the ability to induce its own translation in a
cancer cell-specific manner or stimulate the immune system
to prevent colonization to a distant site. We are optimistic

23. that as the field of gene therapy continues to advance,
current impediments to effective systemic therapy, such as
non-specific targeting, trapping in organs such as the liver,
and neutralization by the immune system, will be overcome
leading to further triumphs in treating cancer. Moreover,
combinatorial approaches using gene therapy with
chemotherapy, small molecule inhibitor therapy, radiation
therapy and/or immunotherapy will lead to further
incremental increases in the efficacy of this approach for the
treatment of diverse human cancers.
But apart from these gene therapy has many scopes to
develop in future.

24. REFERENCES
1. NCERT textbook class- xii
2. Arihant Biology
3. www.cancer.gov
4. www.ncbi.nlm.nih.gov
5. gene-therepy-future.blogspot.in
6. MTG biology