Hall marks of Cancer

1. THE HALLMARKS OF CANCER
Presented by :
Shamanth Neralagundi H.G
Research Scholar

2. What is cancer?
Abnormal cell growth (neoplasia)
Tumour divided into two types
Benign: slow growth, non-invasive, no metastasis
Malignant: rapid growth, invasive, potential for
metastasis
Cancers originate from a single cell

3. What causes the mutations that lead to cancer?
Viruses: HPV --> cervical cancer
Bacteria: H. pylori --> gastric cancer
Chemicals -->Nicotine --> lung cancer
UV and ionizing radiation --> skin cancer

4. Mutagens
•Viruses: insertional mutagenesis
•Chemicals: DNA adducts
•UV and ionizing radiation: single
and double strand DNA breaks

5. What types of genes get mutated in cancer?
•Oncogenes are activated
Normal function: cell growth, gene
transcription
•Tumor suppressor genes are inactivated
Normal function: DNA repair, cell cycle
control, cell death

6. What are the differences in the
features of normal and cancer cells

7. Hallmarks of Cancer
Six fundamental changes
1. Self sufficiency in growth factors
2. Insensitivity to growth-inhibitory
signals
3. Evasion of apoptosis
4. Limitless replicative potential
5. Sustained angiogenesis
6. Ability to invade and metastasize

8. Self sufficiency in growth signals
Dependence on growth signal can be seen in normal cells but
in cancer cells they have got autonomy in synthasis of
growth singnals
Receptors over expression may enable the cancer cell to
become hyperrseponsive to ambient level of growth factors
(ERG-R/erbB) is upregulated in stomach ,brain and breast
tumors
Ligand independent signaling can be achieved through
structural alteration of recptors
Ras protiens are present in structurally altered forms that
enable them to release a flux of mitogenic signals into cells

9. Intracellular signalling
Growth factors
Growth factor receptors
Cell wall

10. Insensitivity to growth-inhibitory signals
Within normal tissue ,multiple antiproliferative signals
operate to mantain cellular quiescence and tissue
homeostasis
Cells monitor their external environment during G1
phase on the basis of signals decides whether to
proliferate or to be quiescent or to enter a post mitotic
state
Disruption of the pRB pathway liberates E2Fs and thus
allows cell proliferation
Over expression of oncoprotien can reverse the process
,there by imparing differentiation and promoting
growth

11. Evading Apoptosis

14. Tumors cannot enlarge beyond 1-2 mm thickness
unless they are vascularized, hypoxia will induce
apoptosis by activation of p53 .
Angiogenesis is required for tumor growth &
metastasis.
Tumor-associated angiogenic factors may be produced
by the tumor or by inflammatory cells
P53 inhibit angiogenesis by stimulation of
anti-angiogenesis molecules
VEGF is under the control of RAS oncogene .
Proteases are involved in regulating angiogenic &
antiangiogenic factors
Development of Sustained Angiogenesis

15. VEGFRFGFR PDGFR
Smooth
muscle Endothelial Blood vessel
Oxygen and
nutrients
Blood vessel
The formation and maintenance of new
blood vessels (angiogenesis) plays a critical
role in tumour growth.
New blood vessels supply the cancer cells
with oxygen and nutrients, allowing the
tumour to grow.
Angiogenesis is mediated principally
through vascular endothelial growth
factor (VEGF)
Other growth factors also play a role, e.g.:
• Fibroblast growth factor (FGF)
• Platelet-derived growth factor (PDGF)

16. Angiogensis activator and inhibitors

17. Ability to Invade & Metastasize
Tumor cells binds to leukocytes, this protect them from
host defense mechanisms
Tumor cells adhere to vascular endothelium & pass
through Basement membrane
Site of extravasations & Meyts depends on:
-Blood & Lymphatic supply
-Organ tropism/adhesion molecules
Function of E-cadherin is lost ,which serves as a
widely acting suppressor of invasion

20. Most normal human cells have a capacity of 60-70
doubling, after the cell will enter non replicative
senescence & result in shortening of telomeres at the
end of chromosome & loss of telomeres beyond a
certain point will lead to massive chrosomal
abnormalities & death
In order to develop tumor, need to maintain cells i.e.
avoid cell senescence
This is done by enzyme TOLEMERASE which
maintain chromosome length
85-95% of cancer have up regulation of enzyme
telomerase
Limitless Replicative Potential

22. Emerging Hallmarks

23. Deregulating cellular energetics

27. Cancer cells environment

28. Targeting the tumour

29. Summary
•Cancer is a disease of Division, growth and spread
•It has a number of causes many of them
preventable
•The survival of the patient is determined by the
stage of the disease, the earlier the detection or the
smaller the tumour the better the survival