targeted theraphy in cancer

1. A Seminar Submitted to :
VIJAYA INSTITUTE OF PHARMACEUTICAL SCIENCES FOR WOMEN
VIJAYAWADA
In Partial Fulfillment of the requirement for the Award of the Degree
BACHELOR OF PHARMACY
Under the guidance of :
Mrs. D.Santhi Krupa , M. Pharm , Asst .professor,
Department of pharmacology
Submitted by :
M. Alekya
137N1R0015
1

2. CONTENTS
INTRODUCTION
EPIDEMOLOGY
SIGNS AND SYMPTOMS
RISK FACTORS
GOALS AND CHALLENGES OF TARGETED CANCER THERAPY
TARGETED THERAPY DEVELOPMENT
TARGETS FOR THERAPY
TREATMENT
SIDE EFFECTS
LIMITATIONS
PRESENT THERAPIES
CONCLUSION
REFERENCES 2

3. INTRODUCTION
• Cancer is a disease which occurs when changes in a group of
normal cells within the body, lead to uncontrolled growth causing
a lump called a tumor.
Classification:
 Carcinoma
 Sarcoma
 Lymphoma
 Leukaemia
3

4. • Targeted cancer therapies include drugs or other substances that
block the growth and spread of cancer by interfering with
specific molecules (molecular targets) that are involved in the
growth, progression , and spread of cancer.
• Targeted therapy is a special type of chemotherapy that
differentiate between the normal cells and cancer cells.
4
Conti..,

5. EPIDEMOLOGY
• According to National Cancer Registry Programme of ICMR,
more than 1300 Indians die every day due to cancer.
• In 2013 : 4,65,169 deaths out of 30,16,628 cases.
• In 2014 : 4,91,598 deaths out of 28,20,179 cases.
• Breast cancer and lung cancer is the most common one.
5

6. SIGNS AND SYMPTOMS
It includes :
Lumps
Coughing and breathlessness
Changes in bowel habit
Bleeding
Unexpected weight loss
Fatigue
6

7. RISK FACTORS
It involves mainly :
• Chemical carcinogens - Asbestos, Tobacco
smoke.
• Age
• Genetics - Genetically inherited diseases.
• Diet - Red processed meat.
• The immune system - Organ transplant and
HIV or AIDS.
7

8. • Obesity – More than 25% overweight and higher
insulin levels.
• Alcohol – It causes mouth ,breast & bowel cancer.
• Tobacco – lung cancer.
• Infection – H. pylori causes stomach cancer.
• Ionising radiation – UV radiations lead to
melanoma , skin cancers.
• Work Place Hazards – mesothelioma.
8
Conti..,

9. GOALS AND CHALLENGES OF
TARGETED THERAPY
• Cure the cancer
• Slow the cancer’s growth
• Kill the cancer cells
• Relieve symptoms caused by cancer
• The drugs works only if the tumor have specific target.
Researchers will developed more targeted drugs that relieves the
side effects caused by targeted therapy.
9

10. TARGETED THERAPY
DEVELOPMENT
• Identification & development of a therapy that promote cancer
cell growth or survival.
• Most targeted therapies are Small molecules and Monoclonal
antibodies.
• Small molecules are developed for targets that are located inside
the cell.
• Monoclonal antibodies are developed by injecting animals with
purified target protiens. 10

11. TARGETS FOR TARGETED CANCER
THERAPY
• Targeted cancer therapies are a type of biological therapy that
aims to target cancer cells directly, they target specific parts of
cells and the signals that cause cancer cells to die naturally.
Targeted therapies targets include:
A. Monoclonal antibodies
B. Small molecule inhibitors
11

12. 12

13. A. MONOCLONAL ANTIBODIES
• In 1975, Kohler & Milstein developed techniques for producing
MoAb’s.
• The first chimeric antibody was Rituximab, was approved by
the US FDA.
• Trastuzumab targets the HER2 oncoprotein. Bevacizumab that
targets VEGF.
13

14. 14

15. B. SMALL MOLECULE INHIBITORS:
• Enzymes and receptors are inhibited by endogenous protien, but
can be also inhibited by small molecule inhibitors which can bind to
the activate site or on the allosteric site.
It includes:
a) TYROSINE KINASE INHIBITORS
b) mTOR INHIBITORS
c) PROTEOSOME INHIBITORS
d) EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITORS
e) SIGNAL-TRANSDUCTION INHIBITORS
f) MULTI-TARGETED KINASE INHIBITORS
15

16. a) TYROSINE KINASE INHIBITORS :
• Tyrosine kinase are specific enzymes that may signal cancer cells to
grow.
• Tyrosine kinase inhibitors are targeted cancer therapies that block
these cell signals. ex- Glivec and Gefitinib
The first TKI’s approved by FDA are:
• ALK Inhibitors - Crizotinib
- Ceritinib
• EGFR Tyrokinase Inhibitors - Gefitinib
16

17. b) mTOR INHIBITORS :
 mammalian Target Of Rapamycin pathway plays an important
role in cell proliferation, growth, and angiogenesis.
 There are two mTOR inhibitors : Temsirolimus , Everolimus.
17

18. c) PROTEOSOME INHIBITORS :
• The Ubiquitin pathway
represents the major pathway for
intracellular protein degradation.
Mechanism :
• Stage 1 - Ubiquitin Tagging
• Stage2- Proteolytic Degradation
18

19. d) EPIDERMAL GROWTH FACTOR RECEPTOR
INHIBITORS:
• EGFR is a protein found on the surface of some cancer cells.
• There are two FDA approved EGFR inhibitors are :
- Afatinib
- Erlotinib
• EGFR inhibitors work by blocking the signals that activate
receptors , this results in decreased tumor growth.
19

20. e) SIGNAL-TRANSDUCTION INHIBITORS :
• During this process, once a cell has received a specific signal,
the signal is relayed within the cell through a series
of biochemical reactions that produce the appropriate
responses.
f) MULTI-TARGETED KINASE:
• Most multi-targeted drugs can suppress the micro-environment
that supports the tumor growth by inhibiting the VEGFR
signal pathway, and thus exert dual anti-angiogenesis and anti-
proliferation effects. 20

21. LIGAND-TARGETED THERAPY:
• Targeting ligands are characterized by synthetic peptide
binding and competition assay.
• Phage display, a selection technique in which a peptide or
protein is expressed as a fusion with a coat protein of
bacteriophage, results in a fusion peptide.
21

22. TREATMENT
 The targeted drugs is given as a pill or
through a vein (IV).
IV drugs are given in these ways :
--Through a syringe, called as IV push.
--Through IV pump for 30 min or few
hours.
--Continuous IV infusions for 7 days.
 Drugs used : Sunitinib and Gleevec.
22

23. SIDE EFFECTS
It involves :
• Skin problems
• Blood clotting and wound healing
• High blood pressure
• Gastrointestinal perforation
• Immuno suppression
• Impaired sperm production
• Diarrhoea, Constipation , Swelling in hands
22

24. LIMITATIONS
• Cancer cells can become resistant to targeted therapy. It is of two
ways- the target itself changes through mutation and tumor finds
the new pathway for tumor growth.
• Targeted therapy in combination with one or more traditional
chemotherapy drugs.
• Drugs for some identified targets are difficult to develop because
of the target’s structure or the way its function is regulated in the
cell.
24

25. PRESENT THERAPIES
• Immunotherapy
• Nanotechnology
• Robotic surgery - Radical prostatectomy
• Proteomic methods
25

26. CONCLUSION
Since the 1950’s significant advances have been made in
the chemotherapeutic management of cancer. Unfortunately,
more than 50% of all cancer patients do not respond to initial
therapy, some will be effected by the chemotherapeutic actions
on the normal healthy cells. So the targeted therapies will prevent
the incidence of unwanted effects, and provides selective, safe
and effective treatment for the cancer.
26

27. REFERENCES
• Riechmann L, Clark M, Waldmann H, Winter G. Reshaping hu-
man antibodies for therapy 1988. Nature., 332: 323-327.
• Slamon D, Pegram M. Rationale for trastuzumab (Herceptin) in
adjuvant breast cancer trials. 2001. SeminOncol., 28: 13-19.
• Harris M. Monoclonal antibodies as therapeutic agents for can-
cer 2004. Lancet Oncol., 5: 292-302.
• Dunn FB. National Cancer Act: leaders reflect on 30 years of
progress. J Natl Cancer Inst 2002; 94: 8-9.
27

28. • Kohler G, Milstein C. Continuous cultures of fused cells secreting
antibody of predefined specificity. Nature 256: 495-497, 1975.
• Liu AY, Robinson RR, Hellstrom KE, Murray ED Jr, Chang C P,
Hellstrom I. Chimeric mouse-human IgG1 antibody that can me-
diatelysis of cancer cells, USA 84: 3439-3443, 1987.
• Adams GP, Schier R, Marshall K, Wolf EJ, McCall AM, Marks JD,
Weiner LM. Increased affinity leads to improved selective tumor
delivery of single-chain Fv antibodies. Cancer Res 1998;58: 485-
490.
27

29. 29

30. 30