Cancer chemoprevention uses natural or laboratory-made substances to prevent cancer from developing. It is typically used by people at higher risk of cancer, such as those with a family history or previous cancer. Some chemopreventive agents studied include tamoxifen, raloxifene, aspirin and other NSAIDs. While chemoprevention may lower cancer risk, it also carries risks of side effects that must be weighed against the individual's cancer risk. Clinical trials test chemopreventive agents' safety and efficacy in delaying or preventing cancer. Targeted drug delivery seeks to concentrate medication in tissues of interest while reducing side effects by specifically targeting cancer cells over normal cells. Strategies include passive,

1. Cancer Chemoprevention
Mohit Kohli

2. Introduction
• Cancer chemoprevention is the use of substances to stop cancer from developing.
• These substances may be natural, made in a laboratory, or taken from a living
source.
• A tumor can be cancerous or benign.
• The transition from a healthy cell to a cancerous one is a process that usually
takes many years.
• Chemoprevention is typically used by people who have a higher risk of
developing cancer.
• People who have had cancer may use chemoprevention to lower the risk of the
cancer.
• The risk of new cancer and the old cancer returning after treatment are high.

3. chemotherapy
• Treatments are provided to kill cancer cells
• Firstly, the staging of cancer is done.
• Chemotherapy incudes whole body treatment.
• Mostly, the injections injected in to vein. And pills taken
• It kills cancerous cells
• It is given in course over weeks and it affects the fast growing cells.
• Type of chemo differs from person to person, and disease.
• Therefore, doctors monitor specific side effects for these.

4. Chemoprevention
• The term "chemoprevention" refers to efforts to prevent or delay the
development of cancer by taking medicines, vitamins or other
agents.
• Tamoxifen and raloxifene: These medicines have been studied as ways to
reduce breast cancer risk. Tamoxifen blocks the effects of estrogen on
tumor growth. It has been shown to lower the risk of breast cancer
recurrence. Raloxifene has been shown to lower the risk of breast cancer
in women who have gone through menopause.
• Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs): May
lower the risk of many types of cancer in people with an average risk of
cancer.

5. Risks and Benefits of Chemoprevention
• For example, drugs that may lower the risk of cancer may increase the
risk of side effects. People with a higher risk of developing cancer
may be willing to accept specific side effects. However, others may
not want to use a drug that gives them side effects when they are not
already sick. Everyone's preferences are different.
• Talk with your doctor about your risk of developing cancer, your
current health status, and your preferences for taking medication. It is
also important to talk with your doctor about how much a type of
chemoprevention may lower your cancer risk. The effect of
chemoprevention seen in research studies may be different for you.

6. Chemoprevention in Clinical Trials
• Animals models are useful but not reliable predictors of activity in
humans
• All drugs or other substances that have shown evidence of lowering
cancer risk are tested in Clinical Trials.
• A chemoprevention-specific study tests a substance to evaluate
whether it is safe and effective in delaying or preventing cancer.
• For example, raloxifene was originally being studied as a way to
strengthen bones. During the study, researchers found that women
taking raloxifene were less likely to get breast cancer.

7. • Another clinical trial of selenium and vitamin E for prostate cancer showed
that neither selenium nor vitamin E lowered the risk of prostate cancer.
And, there was evidence that men who took vitamin E had an increase in
prostate cancer.
• Clinical trials often reveal that chemopreventive substances do not work
for every person.
• When evaluating the results of chemoprevention clinical trials, it is
important to look at the group of participants. Often, people participating
in these types of clinical trials have known, increased risks for cancer, such
smoking or having a family history of cancer, so the results of the study
may not be applicable to everyone.

8. Molecular Targeting
and Drug Delivery for
Cancer

9. Introduction
• Targeted drug delivery system is a special form of drug delivery
system where the medicament is selectively targeted or delivered
only to its site of action or absorption and not to the non-target
organs or tissues or cells.
• Targeted drug delivery seeks to concentrate the medication in the
tissues of interest while reducing the relative concentration of the
medication in the remaining tissues.
• Improves efficacy and reduce side effects.

10. The drug may be delivered to:
• The capillary bed of the active sites,
• To the specific type of cell (or) even an intracellular region; Ex: Tumors
cells but not to normal cells,
• To a specific organ (or) tissues by complexion with the carrier that
recognizes the target.

11. REASON FOR DRUG TARGETING:
• Drug may arrive at a non-target organ.
• Drug concentrations could be diluted to the point where it has no effect
• Pharmaceutical drug instability in conventional dosage form
solubility,
biopharmaceutical low absorption,
high-membrane bounding,
biological instability,
pharmacokinetic / pharmacodynamics short half-life,
large volume of distribution,
low specificity,
Low therapeutic index.

12. IDEAL CHARACTERISTICS:
1. It should be nontoxic, biocompatible, biodegradable, and physicochemical
stable in vivo and in vitro.
2. It should restrict drug distribution to target cells or tissues or organs and should
have uniform capillary distribution.
3. There should be controllable and predicate rate of drug release.
4. Drug release should not affect the drug action.
5. There should be therapeutic amount of drug release.
6. There should be minimal drug leakage during transit.
7. Carriers used must be bio-degradable or readily eliminated from the body
without any problem and no carrier induced modulation of diseased state.
8. The preparation of the delivery system should be easy or reasonably simple,
reproductive and cost effective.

13. CARRIER OR MARKERS:
• Targeted drug delivery can be achieved by using carrier system. Carrier is one of
the special molecules or system essentially required for effective transportation
of loaded drug up to the pre-selected sites. They are engineered vectors, which
retain drug inside or onto them either via encapsulation and/ or via spacer
moiety and transport or deliver it into vicinity of target cell. Pharmaceutical
carriers:
1. Polymers
2. Microcapsules
3. Microparticles
4. Lipoproteins
5. Liposomes
6. Micelles
7. Dendrimers
8. Virosome
9. Nanoparticle

14. STRATEGIES OF DRUG TARGETING
• Passive Targeting:
Drug delivery systems which are targeted to systemic circulation are
characterized as Passive delivery systems. In this technique drug targeting
occurs because of the body’s natural response to physicochemical
characteristics of the drug or drug carrier system.
• Inverse Targeting:
In this type of targeting attempts are made to avoid passive uptake of
colloidal carrier by RES (Reticulo Endothelial Systems) and hence the process
is referred to as inverse targeting. To achieve inverse targeting, RES normal
function is suppressed by pre injecting large amount of blank colloidal
carriers or macromolecules like dextran sulphate. This approach leads to
saturation of RES and suppression of defense mechanism. This type of
targeting is an effective approach to target drug(s) to non-RES organs.

15. • Active Targeting:
In this approach carrier system bearing drug reaches to specific site on
the basis of modification made on its surface rather than natural uptake
by RES. Surface modification technique include coating of surface with
either a bio adhesive, nonionic surfactant or specific cell or tissue
antibodies (i.e. monoclonal antibodies) or by albumin protein. 3 Types:
a)First order targeting (organ compartmentalization).
b)Second order targeting (cellular targeting).
c)Third order targeting (intracellular targeting).
• Ligand Mediated Targeting:
It is achieved using specific mechanisms such as receptor dependent
uptake of natural LDL particles and synthetic lipid microemulsions of
partially reconstituted LDL particles coated with the apoproteins.

16. • Physical Targeting:
In this type of targeting some characteristics of environment changes
like pH, temperature, light intensity, electric field, and ionic strength
small and even specific stimuli like glucose concentration are used to
localize the drug carrier to predetermined site. This approach was
found exceptional for tumor targeting as well as cytosolic delivery of
entrapped drug or genetic material.
• Dual Targeting:
In this targeting approach carrier molecule itself have its own
therapeutic activity and thus increase the therapeutic effect of drug.
For example, a carrier molecule having its own antiviral activity can be
loaded with antiviral drug and the net synergistic effect of drug
conjugate was observed.

17. TYPES OF TARGETED DRUG DELIVERY SYSTEM
• Nanoparticle:
Nano Tubes: They are hollow cylinder made of carbon, atoms which can be filled and
sealed for potential drug delivery.
Application: Cellular scale needle for attaching drug molecule to cancer cells as an
electrode in thermo cells.
Nano wires: The nanowire pinpoint damage from injury and stroke, localize the cause of
seizures, and detect the presence of tumors and other brain abnormalities.
Application: Technique has potential as a treatment for Parkinson's and similar
diseases.
Nanoshells: Nanoshells are hollow silica spheres covered with gold. Scientists can attach
antibodies to their surfaces, enabling the shells to target certain shells such as cancer
cells.
Application: Technique has potential for targeting cancerous drug.

18. • Dendrimers:
Dendrimers precisely defined, synthetic nanoparticles that are approximately 510
nm in diameter. They are made up of layers of polymer surrounding a control core.
The dendrimers surface contains many different sites to which drugs may be
attached.
Application: In gene transfection, medical imaging
• Liposomes:
Liposomes are small artificially designed vesicles composed of phospholipid
bilayers surrounding with the size ranging from 20 to 10 000 nm. Many
liposome formulations are rapidly taken up by macrophages and this can be
exploited either for macrophage-specific delivery of drugs or for passive drug
targeting which allow slow release of the drug over time from these cells into
the general circulation. The drug molecules can either be encapsulated in aqueous
space or intercalated into the lipid bilayers. The extent of location of drug will
depend upon its physico-chemical characteristics and composition of lipids.
Cationic liposomes and lipoplexes have been extensively researched for their
application in non -viral vector mediated gene therapy.

19. • Transferosomes: A transferosomes, in functional terms, may be
described as lipid droplets of such deformability that permits its easy
penetration through the pores much smaller than the droplets size.
Transferosomes is a supramolecular entity that can pass through a
permeability barrier and there by transport material from the other
site. These are more elastic than standard liposomes.
• Lipoproteins: Lipid particles such as LDL and HDL containing a lipid
and an apoprotein moiety is termed as natural targeted liposomes
and its core can be used to incorporate lipophilic drugs or
lipophilic pro-drugs and it does not require covalent bonding with
the drug. Modifications at the level of glycolipid incorporation can
be used to introduce new targeting moieties. The majority of the
research on the use of LDL and HDL particles has been done
and improved at the level of targeting the drugs to the liver.

20. ADVANTAGES
• Drug administration protocols may be simplified.
• Toxicity is reduced by delivering a drug to its target site, thereby reducing
harmful systemic effects.
• Drug can be administered in a smaller dose to produce the desire effect.
• Avoidance of hepatic first pass metabolism.
• Enhancement of the absorption of target molecules such as peptides and
particulates.
• Dose is less compared to conventional drug delivery system.
• No peak and valley plasma concentration.
• Selective targeting to infections cells that compare to normal cells.

21. DISADVANTAGES
• Rapid clearance of targeted systems.
• Immune reactions against intravenous administered carrier systems.
• Insufficient localization of targeted systems into tumor cells.
• Diffusion and redistribution of released drugs.
• Requires highly sophisticated technology for the formulation.
• Requires skill for manufacturing storage, administration.
• Drug deposition at the target site may produce toxicity symptoms.
• Difficult to maintain stability of dosage form. E.g.: Resealed erythrocytes
have to be stored at 40 C.
• Drug loading is usually law. E.g. As in micelles. Therefore it is difficult to
predict /fix the dosage regimen.

22. Targeted therapies that have been approved
The FDA has approved targeted therapies for the treatment of some
patients with the following types of cancer:
• Adenocarcinoma of the stomach or gastroesophageal junction:
Trastuzumab Herceptin®), ramucirumab (Cyramza™)
• Basal cell carcinoma: Vismodegib (Erivedge™)
• Brain cancer: Bevacizumab (Avastin®), everolimus (Afinitor®)
• Giant cell tumor of the bone: Denosumab (Xgeva®)
• Kidney cancer: Bevacizumab (Avastin®), sorafenib (Nexavar®),
sunitinib (Sutent®), pazopanib (Votrient®)

23. • Lung cancer: Bevacizumab (Avastin®), crizotinib (Xalkori®), erlotinib (Tarceva®), gefitinib (Iressa®),
afatinib dimaleate (Gilotrif®), ceritinib (LDK378/Zykadia), ramucirumab (Cyramza™)
• Lymphoma: Ibritumomab tiuxetan (Zevalin®), denileukin diftitox (Ontak®), brentuximab vedotin
(Adcetris®), rituximab (Rituxan®), vorinostat (Zolinza®), romidepsin (Istodax®), bexarotene
(Targretin®), bortezomib (Velcade®), pralatrexate (Folotyn®), lenaliomide (Revlimid®), ibrutinib
(Imbruvica™), siltuximab (Sylvant™), idelalisib (Zydelig®), belinostat (Beleodaq™)
• Melanoma: Ipilimumab (Yervoy®), vemurafenib (Zelboraf®), trametinib (Mekinist®), dabrafenib
(Tafinlar®), pembrolizumab (Keytruda®), nivolumab (Opdivo®)
• Multiple myeloma: Bortezomib (Velcade®), carfilzomib (Kyprolis®), lenaliomide
(Revlimid®),pomalidomide (Pomalyst®)
• Myelodysplastic/myeloproliferative disorders: Imatinib mesylate (Gleevec®), ruxolitinib
phosphate (Jakafi™)
• Ovarian epithelial/fallopian tube/primary peritoneal cancers: Bevacizumab (Avastin®),olaparib
(Lynparza™)
• Pancreatic cancer: Erlotinib (Tarceva®), everolimus (Afinitor®), sunitinib (Sutent®)
• Prostate cancer: Cabazitaxel (Jevtana®), enzalutamide (Xtandi®), abiraterone acetate (Zytiga®),
radium 223 chloride (Xofigo®)
• Soft tissue sarcoma: Pazopanib (Votrient®)

24. CONCLUSIONS
Delivery of drug molecule to reach its specific site is itself a difficult task in
the complex cellular network of an organism. Finally, targeted drug delivery
is coming forward as one of the brightest advanced technique in the
medical sciences in the diagnosis and treatment of couple of lethal
diseases, specially cancer. It has crossed the infancy period and now
touching height of growths in research and development in clinical and
pharmaceutical fields. Overall, it may be concluded with the vast
database of different studies, the science of site specific or targeted
delivery of these drugs has become wiser and intelligent with time and
the advancement of scientific technology. Manifestation of all these
strategies and advanced technologies in clinical field leads to new era of
therapeutic and diagnostics in future.