neoplasm

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NEOPLASM
SUPERVISOR
Dr. dr. Nugraha Utama Pelupessy, SpOG(K)

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1. BIOLOGI AND GENETICS
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Growth Regulation
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PROLIFERATION
• The number of cells in normal tissues is
tightly regulated by a balance between
cellular proliferation and death.
• Dysregulation of cellular proliferation is
one of the main hallmarks of cancer. There
may be increased activity of genes
involved in stimulating proliferation
(oncogenes) or loss of growth inhibitory
(tumor suppressor) genes or both.

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Growth Regulation
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CELL DEATH
Apoptosis
Necrosis
Autophagy

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Origins of Genetic Alterations
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Genetic damage may be inherited or may arise after birth as a result of either exposure to
exogenous carcinogens or endogenous mutagenic processes within the cell

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Origins of Genetic Alterations
• Although most cancers arise sporadically in the population because of acquired genetic damage,
inherited mutations in cancer susceptibility genes are responsible for some cases.
Inherited Cancer Suscepbility
• The etiology of acquired genetic damage in cancers also has been elucidated to some extent
Acquired Genetic Damage
• Epigenetics changes are heritable changes that do not result from alterations in DNA sequence
Epigenetic Changes
• Cell Membrane Oncogenes—Peptide Growth Factors and Their Receptors
• WNT Pathway
• Intracellular Oncogenes
• Nuclear Oncogenes
Oncogenes
• Nuclear Tumor Suppressor Genes
• Extranuclear Tumor Suppressor Genes
• MicroRNA
Tumor Suppressor Genes

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Invasion and Metastasis
• Metastasis is a process by which cancer cells spread from the
primary tumor to distant sites.
• It is now appreciated at a molecular level that metastasis is
dependent on a balance between stimulating factors from both
the tumor and host cells versus inhibitory signals.
• To produce metastasis, the balance must be weighted toward the
stimulatory signals.

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Gynecologic Malignancies
1. Endometrial Cancer

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Gynecologic Malignancies
2. Ovarian Cancer

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3. Cervical Cancer
Gynecologic Malignancies
Etiology
Unlike most other types of human cancers that occur because of mutations in oncogenes and tumor suppressors, cervical cancers arise as a
consequence of viral inactivation of the TP53 and RB tumor suppressors by the HPV E6 and E7 oncoproteins, respectively
Secondary Genomic Changes
HPV associated cervical carcinogenesis with inactivation of the TP53 tumor suppressor gene leads to genomic instability that results in secondary
genetic alterations that play a role in the development and phenotype of these cancers
4. Gestational Trophoblastic Neoplasia
The most prominent feature of these tumors is an imbalance of parental chromosome s.

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2. Biologic, Targeted,
And Immune Therapy
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Biologic and Targeted Therapies
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The growth of cancer cells is crucially dependent on oncogenic signal transduction
pathways. Extracellular signals are transmitted to the cancer cell via transmembrane
receptors.
Novel therapeutics are targeted to modulate these signal transduction pathways by
blocking the extracellular transmembrane receptors or interfering with intracellular
proteins such as tyrosine kinases further downstream.
Targeting the signaling cascade inhibits the proliferation of cancer cells, induces
apoptosis, and blocks metastasis.

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Biologic and Targeted Therapies
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Biologic and Targeted Therapies
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• is a complex process that is influenced by various pro- and antiangiogenic factors, including VEGF,
interleukin 8, platelet-derived endothelial cell growth factor, and angiopoietins. Overexpression of these
angiogenic factors leads to neovascularization and increased supply of nutrients and oxygen to the
tumor.
Angiogenesis
• VEGF is overexpressed in gynecologic malignancies, therefore presenting an excellent target for therapy
Vascular Endothelial Growth Factor
• The epidermal growth factor receptor pathway plays an important role in regulation of growth and
differentiation of epithelial cells through regulation of cell division, migration, adhesion, differentiation,
and apoptosis
Epidermal Growth Factor Receptor

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• The HER2/neu receptor is activated by homo- or heterodimerization, resulting in tyrosine
phosphorylation and subsequent activation of various downstream signals that among other functions
control cellular proliferation, migration, and invasion.
HER2/neu
• The mitogen-activated protein (MAP) kinase cascades are activated by various cofactors, inflammatory
cytokines, and stress
Mitogen-activated Protein Kinase Pathways
• The enzyme poly (adenosine diphosphate-ribose) polymerase (PARP) and the BRCA proteins are
involved in DNA repair as induced by cytotoxic agents like platinum chemotherapy or radiation.
PARP Inhibitors
• Activation of this pathway can be demonstrated in more than 80% of endometrial cancers, 50% to 70%
of epithelial ovarian cancers, and approximately 50% of cervical cancers
The PI3-kinase/Akt/mTOR Pathway
Biologic and Targeted Therapies

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Immunotherapy
Failure of functional immunity contributes to the genesis of virus-associated cancers, Although many
effective induced antitumor immune responses have been described, the relative role of natural antitumor
immune responses in the detection and destruction of cancer cells.
Components of the Immune System
Involved in Antitumor Responses

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Therapeutic Strategies
• Cancers may develop or progress because immune cells are not given
a strong enough signal to become activated and destroy the tumor
cells, It may be possible to counter this lack of antitumor immune
responsiveness by enhancing antigen presenting cell (APC) activity,
providing tumor-associated antigens in a manner that can better
induce the generation of antitumor effector T cells (tumor vaccine
therapy), or both.
Cancer Vaccines
• vaccines human papilloma virus (HPV)
Cervical cancer
• One of the candidate antigen for vaccine development is NY-ESO-1
• Other vaccination strategies have used p53 peptides as the
immunogenic antigen,
Ovarian Cancer

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Thank You