Mekanisme Seluler

“Kanker”
Biologi Sel Dasar
Farmasi Unisba
2018
Persiapan Diskusi
O Buat kelompok yang terdiri dari 4 orang mahasiswa!
O Masing-masing kelompok akan diberikan naskah
artikel yang menjelaskan tentang mekanisme
seluler terbentuknya sel kanker.
O Diskusi diawali dengan penjelasan singkat tentang
proses terbentuknya sel kanker dilanjutkan dengan
diskusi/dinamika kelompok yang dipandu oleh dosen
pengajar
Bahan Diskusi
O Temukan istilah-istilah yang menjadi menurut Anda menjadi kata
kunci dalam proses terbentuknya kanker!
O Petakan struktur apa saja yang terlibat dalam proses-proses
terbentuknya kanker!
O Apa peran dari masing-masing struktur yang terlibat dalam
proses terbentuknya kanker?
O Diskusikan dengan kelompok Anda, titik kritis yang menjadi faktor
penentu dalam proses terbentuknya kanker!
O Tentukan pula upaya yang dilakukan dalam mencegah terbentuknya
sel kanker!
O Apa rekomendasi Anda dalam menangani kanker berdasarkan proses
terbentuknya sel kanker tersebut? Saran Anda dapat berupa
rancangan obat yang dapat mengatasi/menghambat proses
pembentukan sel kanker.
Capaian Pembelajaran

Memahami mekanisme seluler

terjadinya kanker

Memahami keterlibatan
komponen-komponen sel dan
fungsinya dalam kanker
An Overview on Cancer
O 1:3 people is likely to suffer from cancer during their lifetime
O Siegel et al. (2011): ± 571, 950 Americans would die from cancer
in 2011, mortality rate (deaths/year/100.000 people) was over
200 for men in the UK in 2008 (Summary June 2011, Cancer
Research, UK)
O The worldwide incidence: ± 12.7 million cases in 2008 (Jemal et
al., 2011)
O Knowledge of the molecular details in important cellular and
biochemical pathways can be applied to a new wave of
cancer therapies
An Overview on Cancer
O Cancer is a group of diseases characterized by
unregulated cell growth and the invasion and
spread of cells from the site of origin, or
primary site, to other sites in the body
O Cancer is considered to be a group of diseases 
over 100 types
O Origin off tissues
O Epithelial tissues (carcinomas)  85%
O Mesoderm tissues (sarcomas)
O Glandular tissue (adenocarcinomas)
An Overview on Cancer
O The major factor that causes cancer in each target
tissue is different: ultraviolet (UV) radiation from the
sun can easily target the skin, while inhalation of
cigarette smoke can target the lungs
O There are differences in the molecular mechanisms
involved in carcinogenesis within each cell type and
the pattern of spread of cells from the primary site
O Treatment must be applied differently
An Overview on Cancer
O In the year 2000, upon fine analysis, Hanahan and Weinberg defined six
hallmarks of most, if not all, cancers
O The capability for autonomous growth signals
O Evasion of growth inhibitory signals
O Evasion of apoptotic cell death
O Unlimited replicative potential
O Angiogenesis (the formation of new blood vessels)
O Invasion and metastasis are essential for carcinogenesis
O Two emerging hallmarks
O Reprogramming energy metabolism
O Avoiding immune destruction
An Overview on Cancer
O Characterized by unregulated cell growth and the
invasion and spread of cells from their site of origin
O Benign tumor: not evidence of cancer, do not spread
throughout the body (do not metastasize), some can be
life threatening (e.g. a benign brain tumor that may be
difficult to remove)
O Malignant tumor, on the other hand, do not remain
encapsulated, show features of invasion, and
metastasize.
Hallmarks of Cancer
O Growth signal autonomy:
O Normal cells need external signals from growth factors to divide
O Cancer cells are not dependent on normal growth factor signaling
O Acquired mutations short-circuit growth factor pathways leading to
unregulated growth.
O Evasion of growth inhibitory signals:
O Normal cells respond to inhibitory signals to maintain homeostasis (most
cells of the body are not actively dividing)
O Cancer cells do not respond to growth inhibitory signals
O Acquired mutations or gene silencing interfere with the inhibitory
pathways.
Hallmarks of Cancer
O Avoiding immune destruction (emerging hallmark):
O There is evidence to support the theory of immune surveillance that states the
immune system can recognize and eliminate cancer cells.
O Successful cancer cells may be those that do not stimulate an immune response or
can interfere with the immune response so as to avoid immune destruction.
O Unlimited replicative potential:
O Normal cells have an autonomous counting device to define a finite number of cell
doublings after which they become senescent. This cellular counting device is the
shortening of chromosomal ends, telomeres, that occurs during every round of DNA
replication
O Cancer cells maintain the length of their telomeres
O Altered regulation of telomere maintenance results in unlimited replicative potential.
Hallmarks of Cancer
O Tumor-promoting inflammation (an enabling characteristic):
O Virtually all tumors contain inflammatory immune cells
O Inflammation is an immune response that can facilitate the ability of acquiring the
core hallmarks of cancer. For example, inflammatory cells can provide growth
factors and enzymes that promote angiogenesis and invasion
O In addition, inflammatory cells can release oxygen species that are mutagenic.
O Invasion and metastasis:
O Normal cells maintain their location in the body and generally do not migrate
O The movement of cancer cells to other parts of the body is a major cause of cancer
deaths
O Alterations of the genome may affect the activity and/or levels of enzymes involved
in invasion or molecules involved in cell–cell or cellular–extracellular adhesion.
Hallmarks of Cancer
O Angiogenesis (formation of new blood vessels):
O Normal cells depend on blood vessels to supply oxygen and nutrients but
the vascular architecture is more or less constant in the adult
O Cancer cells induce angiogenesis, the growth of new blood vessels,
needed for tumor survival and expansion
O Altering the balance between angiogenic inducers and inhibitors can
activate the angiogenic switch.
O Genome instability and mutation (an enabling characteristic):
O Acquiring the core hallmarks of cancer usually depends on genomic
alterations
O Faulty DNA repair pathways can contribute to genomic instability.
Hallmarks of Cancer
O Evasion of cell death:
O Normal cells are removed by apoptosis, often in response to DNA
damage
O Cancer cells evade apoptotic signals.
O Reprogramming energy metabolism (emerging hallmark):
O Uncontrolled cell division demands increases in fuel and biosynthetic
precursors that is obtained by adjusting energy metabolism
O Unlike normal cells, cancer cells carry out glycolysis even in the
presence of oxygen. Glycolysis intermediates can be used in
biosynthetic pathways.