Brain Cancer

Biology of
Brain Cancer
NATALIA MARTINS HOFFMANN
Definition
Brain tumors are in reality a very diffuse
collection of tumors of the central nervous
system.
Each of these tumors has a distinct biology,

prognosis, and therapeutic approach.
Brain Cancer
Significance
Risk of Developing Cancer:
Approximately 0.6 percent of men and
women will be diagnosed with nervous
system cancer .
Brain Cancer
Lifetime
Tumors
of the CNS account for less than

2% of all global malignancies.
Particularly
devastating: often affect

children and young adults. Frequently
lead to mental impairment or death.
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Singularity
Brain Cancer
biology of the brain

difficult treatment
Unique
Organ
is enclosed in a bony canal: little room

for growth; compression and damage.
Many
tumors extensively invade the brain.

Complete surgical removal impossible.
brain
cancer cells are protected behind a

blood-brain barrier. Disruption=edema, poorly
tolerated (few space, lack of lymphatics).
Etiology
The causes of CNS are complex not completely known
Risk factors unclear. medical condictions and

medicines, overweight, power line, mobile phones..
Increase (?)
A small proportion of brain tumours are related to

Hereditary syndromes
Neurofibromatosis
Von
Hippel-Lindau disease (VHL gene)
Tuberous
Li
(NF gene)
sclerosis
Fraumeni syndrome (p53)
Brain Cancer
Gliomas
most common malignant brain tumours (>50%).
Any tumor that arises from the glial - supportive tissue

of the brain.
Glial cells maintainhomeostasis, formmyelin,

support and protection forneuronsandperipheral
nervous.
http://www.ncbi.nlm.nih.gov/books/NBK10869/figure/A53/?report=objectonly
Brain Cancer
Classification according to origin
Non Glial origin (structures out of brain parenchyma)
Meninges
Cranial Nerve
Pituitary
Pineal
Glial origin: Gliomas
Astrocytomas
Oligodendrogliomas
Ependymomas
Mixed (oligoastrocitomas)
Brain Cancer
Brain Cancer and Metastasis
They
brain tumors rarely metastasize.
Brain Cancer
Primary
may widely infiltrate the nervous system.
Metastatic
brain tumors much more common

than primary brain tumors.
Brain
metastases occur in 20% to 40% of

cancer patients.
6
Brain Cancer and Metastasis

common tumors: lung cancer, unknown
primary, breast, melanoma, renal, and colon
cancers.
Prognosis
no greater than 1-5 months.
Approx.
80% of metastases in cerebral

hemisphere, 17% in the cerebellum and 3% in
the brain stem
The
histopathologic features similar to that of

tumor of origin.
Brain Cancer
Most
Primary Brain Cancer

multiforme
Brain Cancer
Glioblastoma
(astrocytoma)
Medulloblastoma
Ependymoma
Glioblastoma multiforme
The
frequent and lethal primary cancer of the CNS
highest grade glioma tumor,
presence
of necrosis and increase of blood vessels

around the tumor
Patient
very
survival at five years less than 5%
resistant to radio and chemotherapy
diffusely
and deeply infiltrates the normal
brain parenchyma
Brain Cancer
most
De
novo tumors: majority of glioblastomas

in persons age 55 and older.
Secondary
glioblastomas, most often

found in patients ages 45 and younger.
typically start as low-grade or mid-grade

astrocytoma
Brain Cancer
The two types of gliobastoma
highly
heterogeneous tumor: includes a

variety of cancer cell types
differentiated stellar morphology (markers:
GFAP and S100)

Small
and rounded undifferentiated cells mixed

with stromal elements
Brain Cancer
Pathology
Medulloblastoma
most common malignant brain
tumor in children
Embryonal
neuroepithelial tumor of the
cerebellum
Express
markers of neuronal and glial

cell lineage (by being embryonal
tumors.)
Approximately
one-third of patients
with MB tumors remain incurable
Spread
through the cerebrospinal fluid
Brain Cancer
The
Ependymomas
from the wall of the
ventricular system
Brain Cancer
Originate
Can
occur along the entire

craniospinal axis.
Occurs
in both in children and
adults
Pathognomonic
symptom: strong
pain in the neck tomor grows
throughout the foramen magnum.
calcifications
Origin and development:
Stem cells
BCPCs:
Ability
Brain cancer propagating cells
Brain Cancer
hypothesis
to self-renew and proliferate
BCPCs
can initiate new tumors in mice with

high efficiency (showing many traits of human
cancer).
Neural
stem cells and BCPCs: defined by the

same surface markers - Nestin and CD133
Isolated
from GBM, MB & ependymoma

1
Development
Brain Cancer
(BCPC)
Ependymal cell
Tumor cells with stem-like properties.
(Trends in Molecular Medicine Vol.15 No.11)
Biomarkers in neuro-oncology
Overcome the limitation in the histopathological
diagnosis.
Prognostic and drog response evaluation
Gliobastoma: promoter methylation of the O6methyguanine methyltransferase (MGMT) gene:
longer length of survival and chemotherapeutic

response.
EGFR
(epidermal growth factor receptor)

overexpression associated with poor survival.
Brain Cancer
Clinical manifestations
First symptoms are usually due to
increased pressure in the brain.
Headaches, seizures, memory loss

and changes in behavior.
Loss in movement or sensation on one side of

the body, language dysfunction and cognitive
impairments.
Depending upon the size and location of

the tumor.
Brain Cancer
21
Treatment
Surgery
Radiation
Chemotherapy early ast. & olig.
Symptoms medication manangement
BIOLOGIC AND TARGETED THERAPIES
specific targeting of BCPCs might potentially be

more effective at treating the entire tumor mass
experimental approaches have targeted

VEGF/VEGF receptors pathway
improved patient survival and quality of life.
Brain Cancer
Thank You!!
Brain Cancer
https://www.youtube.com/watch?v=hXLh3CQa9XE
References
Costas G. Hadjipanayis, Erwin G. Van Meir. Brain cancer propagating cells:
biology, genetics and targeted therapies. Trends in Molecular Medicine
Vol.15 No.11. Elsevier doi:10.1016/j.molmed. 2009.09.003
Pter Molnr. Classification of Primary Brain Tumors: Molecular Aspects.

Availeble on http://cdn.intechopen.com/pdfs-wm/20839.pdf. Accessed in
03/2015
AMERICAN BRAIN TUMOR ASSOCIATION. Glioblastoma and Malignant

Astrocytoma. Availeble on http://www.abta.org/secure/glioblastomabrochure.pdf. Accessed in 03/2015.
RobertWechsler-Reya & Matthew P. Scott. THE DEVELOPMENTAL BIOLOGY

OF BRAIN TUMORS. Annu. Rev. Neurosci. 2001. 24:385428
Konstantina A. Svokos , Bodour Salhia Steven A. Toms, Molecular Biology

of Brain Metastasis. Int. J. Mol. Sci. 2014, 15, 9519-9530;
doi:10.3390/ijms15069519
Raymond W. Ruddon. Cancer biology. 4. ed. Oxford University Press. 2007
Brain Cancer

Brain Cancer

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Biology of

Each of these tumors has a distinct biology,

of the CNS account for less than

devastating: often affect

biology of the brain

is enclosed in a bony canal: little room

tumors extensively invade the brain.

cancer cells are protected behind a

Risk factors unclear. medical condictions and

A small proportion of brain tumours are related to

Hippel-Lindau disease (VHL gene)

Fraumeni syndrome (p53)

Any tumor that arises from the glial - supportive tissue

Glial cells maintainhomeostasis, formmyelin,

Classification according to origin

Non Glial origin (structures out of brain parenchyma)

Glial origin: Gliomas

Brain Cancer and Metastasis

brain tumors rarely metastasize.

may widely infiltrate the nervous system.

brain tumors much more common

metastases occur in 20% to 40% of

Brain Cancer and Metastasis

no greater than 1-5 months.

80% of metastases in cerebral

histopathologic features similar to that of

Primary Brain Cancer

frequent and lethal primary cancer of the CNS

highest grade glioma tumor,

of necrosis and increase of blood vessels

survival at five years less than 5%

resistant to radio and chemotherapy

and deeply infiltrates the normal

novo tumors: majority of glioblastomas

glioblastomas, most often

typically start as low-grade or mid-grade

The two types of gliobastoma

heterogeneous tumor: includes a

differentiated stellar morphology (markers:

GFAP and S100)

and rounded undifferentiated cells mixed

neuroepithelial tumor of the

markers of neuronal and glial

through the cerebrospinal fluid

occur along the entire

in both in children and

Origin and development:

Brain cancer propagating cells

to self-renew and proliferate

can initiate new tumors in mice with

stem cells and BCPCs: defined by the

from GBM, MB & ependymoma

Tumor cells with stem-like properties.

(Trends in Molecular Medicine Vol.15 No.11)

Prognostic and drog response evaluation

Gliobastoma: promoter methylation of the O6methyguanine methyltransferase (MGMT) gene:

longer length of survival and chemotherapeutic

(epidermal growth factor receptor)