Cancer and its Genetics treatments,Nanomediciens

3. Gene Therapy
The future of cancer
treatment
*MD SAQUIB NASIR KHAN
*STUDENT OF BIOINFORMATICS
BHARATH UNIVERSITY

4. Cancer is a disease of cells. A single cell moves down the
path toward cancer as the result of a series of
environmentally induced changes to critical genes. The
genes affected in cancer may fall into any of three classes
(Craig, 1995). One class comprises the so-called
―oncogenes‖, the genes that code for proteins that promote
cell proliferation. Another class called tumor suppressors
encode proteins that provide a protective role in the body.
A third class is represented by the gene Bcl-2 and consists
of genes that influ-ence cell viability or cell death. The
significance of the third class is that it suggests that cancer
can result not only from the overgrowth of cells, but also
from a lack of cell death.
1. Introduction Of Cancer

6. No. of % of all
Rank Cause of Death deaths deaths
 1. Heart Diseases 631,636 26.0

 2. Cancer 559,888 23.1
 3. Cerebrovascular diseases 137,119 5.7

 4. Chronic lower respiratory diseases 124,583 5.1

 5. Accidents (unintentional injuries) 121,599 5.0

 6. Diabetes mellitus 72,449 3.0

 7. Alzheimer disease 72,432 3.0

 8. Influenza & pneumonia 56,326 2.3

9. Nephritis* 45,344 1.9
US Mortality, 2006
 10. Septicemia 34,234 1.4
*Includes nephrotic syndrome and nephrosis.
Source: US Mortality Data 2006, National Center for Health Statistics, Centers for Disease Control and Prevention,
2009.

7. Japan, year 2000
Annual deaths from smoking
• Smoking kills about 113,000 people a year in
Japan
 About 33,000 die in middle age from smoking
 Many of those killed in middle age would have lived
on for 10, 20, 30 or more good years
 About 22 years of life are lost, on average, by those
killed in middle age by smoking
www.deathsfromsmoking.net

8.  (According to prevantionweb.net)
 No of events:157
 No of people killed:8,568
 Average killed per year:276
 No of people affected:3,361,979
 Average affected per year:108,451
IN JAPAN NATURAL DISASTER

10. hereditary cancers
Difficulties in studying hereditary cancers
*Humans have small families
*Generation times are long
*Highly mobile; hard to keep in touch
*Studies require cooperation
**Consent for tests
**Correct information on family members
*Cancers are different diseases
*Cancers can occur at random; hard to find affected families
*More than one gene must be altered to get cancer

11.  cellular and nuclear pleomorphism,
 they exhibit abnormal mitoses and
chromosomal abnormalities.
 malignant transformation
 Hyperplasia
 Genome instability
 Incresed Angiogenisis
 Incresed motility
Why its hard to identify cancer cell

12. Cancer is disease of
Genes
*Cancer is a genetic disease
−Not monogenic like MD or CF, but multigenic
*Cancer is caused by mutations in somatic cells
*Cancer can be caused by mutagens, chemicals that damage
DNA, or viruses
*Cancer is caused by an accumulation of mutations in different
genes in a single cell
*Cancer is caused by altered expression of genes or by
accumulation of mutations in a single cell

13. Detection of cancers
1.gene tests available:
BRCA1: breast and ovarian cancer
BRCA2: breast cancer
p53: Li-Fraumeni syndrome
APC: FAP colon cancer
MLH1, MSH2 and other DNA repair genes: HNPCC
colon cancer
2. Protein and enzyme tests

14. 3. X-rays: Expose region to low dose X-
rays, obtain image of more dense
regions, including bones and the
accumulation of minerals at tumor sites.
◦ improvements: minimize X-ray dose;
◦ standardize procedures and training to improve
reliability;
◦ use high contrast dyes to localize regions
4.CT or CAT scan--computed tomography--
computer analysis of scanning X-ray images
Cont…..

15. 5.MRI--magnetic resonance imaging--
computer analysis of images that does
not involve X-rays. Involves radiowaves
and deflection by a powerful magnet;
useful for tumors surrounded by bone.
6.ultrasound--lower cost, lower resolution
imaging. Widely used in breast cancer
and prostate cancer to clarify results of
initial tests.
Cont….

16.  replacement gene therapy
 knockout gene therapy
 suicide gene therapy
 immunomodulatory gene therapy
Gene therapy of Cancer

17.  Replacement Gene Therapy=method
for replacing a mutated or missing gene
(usually a tumor suppressor gene) that
serves to keep cell growth and division
under control with a "healthy" (normal)
copy of that gene.
Replacement Gene Therapy

18.  Knockout gene therapy primarily targets
the products of oncogenes in an effort to
inactivate them and reduce cellular
proliferation. Several approaches are being
tried:

 delivering a mutant oncogene that acts in a
dominant manner to negate the effects of the
cancer-causing oncogene
 inhibiting translation of the oncogene by
gene therapy
Knockout gene therapy

19.  Suicide gene therapy—involves the
transduction of a gene that transforms a
nontoxic form of a drug (that is, a "pro-
drug") into a toxic substance.
Suicide gene therapy

20.  Immunomodulatory gene therapy--is a method to induce
cellular immune responses to metastatic tumors. The strategy
involves injecting into the skin of a patient a suspension of
irradiated tumor cells that have been transduced with a cytokine
gene to stimulate a systemic immune response against tumor-
specific
 antigens—in effect, vaccinating the patient against that specific
cancer.

 The basic idea of immunotherapy is to:

 modify tumor cells outside the body with a cytokine gene
 transplant the cytokine-gene modified cells back into the patient
(after the cells have been irradiated to prevent further cell
division)
 let the host's system create an antitumor immune response
Immunomodulatory gene therapy-

21.  Nanomedicine is the medical application
of nanotechnology .Nanomedicine ranges
from the medical applications
of nanomaterials,to nanoelectronic biosensor
s, and even possible future applications
of molecular nanotechnology. Current
problems for nanomedicine involve
understanding the issues related
to toxicity and environmental
impact of nanoscale materials. One
nanometer is one-millionth of a millimeter.
Nanomedicine

22. Nanomedicin
e
Nanomedicine treatment pathway in
blood stream

23. Improving Cancer Treatment
Traditional Treatment Nanotechnology Treatment
Drugs
Toxins Nanodevices
Cancer
Cancer cells Toxins
cells
Noncancerous cells Noncancerous cells
Dead Dead
cancer cancer
cells cells
Dead noncancerous Intact noncancerous
cells cells

24. Polymeric nanoparticles are shown as representative
nanocarriers (circles). Passive tissue targeting is achieved
by extravasation of nanoparticles (NP) through increased
permeability of the tumor vasculature and ineffective
lymphatic drainage (EPR effect).
Active cellular targeting (inset)
can be achieved by
functionalizing the
surface of NP with
ligands that promote
cell-specific recognition
and binding. The nanoparticles can (i) release their contents in close
proximity to the target cells; (ii) attach to the membrane of the cell and act
as an extracellular sustained-release drug depot; or (iii) internalize into the
cell.
Mechanisms by which
Nanocarriers Can Deliver Drugs to
Tumors

25. Nanotechnology Based Drug Delivery
Systems for Cancer Therapy
Schematics - Reproduced from Sahoo and Labhasetwar, 2003 with kind permission from Drug Discovery
Today.
http://www.cancer-therapy.org/CT3A/HTML/13.%20Orive%20et%20al,%20131-138%20.html 2005

26.  ABI1, ABL2, ACSL6, AF1Q, AF5Q31 , AKT1, ARNT, ASPSCR1, ATF1
, ATIC, BCL10, BFHD, BIRC3, BMPR1A, BTG1, CBFA2T1, CBFA2T3,
CBFB, CCND1, CDC2, CDK4,CHIC2, CHN1, COPEB, COX6C, CTNN
B1, CYLD, DDB2, DDIT3, DEK, Eif4a, EIF4A2, EPS15, ERCC2, ERC
C3, ERCC5, ERG, ETV4, ETV6, EWSR1, EXT1, EXT2, FANCC, FANC
G, FGFR1OP,FGFR3, FH, FIP1L1, FUS, GAS7, GATA1, GMPS, GOLG
A5, GPC
(gene), GPHN, HIST1H4I, HRAS, HSPCA, IL21R, IIRF4, KRAS2, LA
SP1, LCP1, LHFP, LMO2, LYL1, MADH4, MEIS1, MLF1,MLH1, MLLT3
, MLLT6, MNAT1, MSF, MSH2, MSN, MUTYH, MYC, NCOA4, NF2, N
PM1, NRAS, PAX8, PCBD, PDGFB, PHOX2B, PIM1, PLK2, PNUTL1,
POU2F1, PPARG, PRCC, PRKACB,PRKAR1A, PTEN, PTPN11, RABEP
1, RAD51L1, RAP1GDS1, RARA, RB1, RET, RHOH, RPL22, SBDS, S
DHB, SEPTIN6, SET, SH3GL1, SS18L1, SSX1, SSX2, SSX4, STAT3,
TAF15, TCF12,TCL1A, TFE3, TFEB, TFG, TFPT, TFRC, TNFRSF6, TP
53, TPM3, TPM4, TRIP11, VHL, WAS, WT1, ZNF198, ZNF278, ZNF
384, ZNFN1A1
Genes involve in cancer treatment

27.  black raspberry are
blueberries, blackberries, strawberries, and
cranberries, These berries are high invitamin
C, fiber, and ellagic acid, which can prevent skin
cancer.
 Tenderstem, help prevent stomach, colon and
lung cancers.
 Broccoli ,Some research has shown that a
serving of broccoli every day can reduce the risk
of colon cancer by almost 50 per cent.
 Cabbage ,Some scientists think cabbage is
particularly good at protecting against colon
cancer and breast cancer.
Natural support for cancer

28.  Watermelon ,Tomatoes, watermelons, guavas and
grapefruit are rich in lycopene. This is a fat-soluble
nutrient which appears to have a powerful action on
the immune system by producing antioxidant activity
in the body.
 Grapes ,An anti-fungal agent found in grapes my
help to protect against cancer, according to
researchers from De Montfort University in Leicester.
Resveratrol is a molecule which helps grapes and
other crops avoid fungus.
 Carrot ,help to prevent retina cancer , which is vary
rear cancer
 Lemon is use to cure against Neuroblastoma
Cont……

29. Video Links
 Cancer Detection with Gold Nanoparticles – May
27, 2007
http://www.youtube.com/watch?v=uyhxRIvw_cY&feature=related
 Nanoparticle Carrying Capacity – March 27, 2008
http://www.youtube.com/watch?v=TVch-fDzet8&feature=related
 Nanotechnology In Drug Delivery - March 16, 2008
http://www.youtube.com/watch?v=ybK5TIGNNFA&NR=1
 Nanomedicine for Brain Tumors – July 3, 2008
http://www.youtube.com/watch?v=gJgmi-D12pk
 Nanomedicine Cancer Drug Delivery from
PlayGenSeriousGames – sponsored by Wellcome
Trust http://www.youtube.com/watch?v=tPAO0WHoaX0 (1st)
February 11, 2008
http://www.youtube.com/watch?v=DEcof9HlUvk (2nd) February
11, 2008 http://www.nanomission.org/ The Game
Site
Play