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Kanker

Penyakit sel dengan ciri gangguan atau


kegagalan mekanisme pengatur multiplikasi
dan fungsi homeostasis lainnya pada
organisme multi seluler.
Characteristics of Neoplastic
Diseases
Normal cells proliferate until normal structural and
functional requirements are met, and are responsive to
feedback control of proliferation
Malignant cells characterized by loss of control of
proliferation, resulting in unneeded populations of cells
that are genetically dysfunctional
Malignant cells can invade tissues (loss of contact
inhibition) and metastasize , or spread to remote sites
Thought to arise from a single cell
Characteristics of Neoplastic
Disease
Most normal cells undergo varying degrees of
differentiation
Malignant cells generally lose these characteristics,
along with structural & functional properties of mature
tissues
Other characteristics of cancer cells: altered
membranes, protein & enzyme content,chromosomal
abnormalities, changes in structural elements
Cancer is a group of 200 - 300 diseases: biological
history & therapeutic response variable
Malignant Transformation
All cellular functions controlled by gene expression
(DNA ==> RNA==> PROTEIN)
Perturbations in this scheme can result in malignancy
due to altered levels or structures of protein
Net result is loss of control of cell proliferation
It is thought that more than one genetic alteration is
required to effect malignant transformation in a given
cell
Cancer arises as an accumulation of changes in a
variety of genes
Sifat Umum Kanker
Pertumbuhan berlebihan ==> tumor
Gangguan diferensiasi => jar. Mudigah
Invasif, mampu tumbuh di jar. sekitar
Bersifat metastatik
Memiliki hereditas/bawaan.
Pergeseran metabolisme ke arah pembentukan
makromolekul dari nukleosida dan asam amino
Peningkatan katabolisme KH untuk energi sel
Bagaimana kanker mengganggu
hospes
Desakan akibat pertumbuhan tumor
Penghancuran jaringan tempat tumor
berkembang dan bermetastasis
Gangguan sistemik akibat sekunder
pertumbuhan sel kanker
Epidemiologi Kanker
Penyebab kematian II pada keseluruhan
populasi
Penyebab kematian I pada:
wanita 30-54 tahun
anak 3-14 tahun
Dengan bedah dan radiasi sembuh 33.3 %
Anti kanker dipakai kuratif pada
Korio karsinoma
Limfoma Burkitt
Tumor Wilms
Sindroma Ewing
Rhabdomiosarkom embrional
Beberapa penyakit Hodgkins
Therapy
Goals of Cancer Therapy:
Curative
Maintenance of quality & duration of life
Symptom relief (palliative treatment)
Clinical trials for experimental therapies
Goals of therapy must be negotiated
between patient, family, physicians and
health care team
Siklus sel kanker
Sedang membelah:
Mitosis M
Paska mitosis G1
Sintesis DNA S
Pra mitosis G2
Istirahat G0
Permanen tidak membelah
CCS dan CCNS
Vinkristin Alkilator
Vinblastin Antibiotik
Merkaptopurin Sisplatin
Hidroksiurea Prokarbazin
Metotreksat Nitrosurea
Asperginase
Contoh pemanfaatan pengenalan
Cell Cycle Spesific
Vinblastin menghentikan sampai siklus M
16 jam kemudian sel dalam fase S
Saat tepat diberikan Sitarabin
Treatment goals depend on :

type of tumor
stage & rate of growth
age & medical condition
economic factors
Therapeutic Modalities

Surgery
Radiation Therapy
Chemotherapy
Endocrine
Biological
Experimental
Chemotherapy
Includes administration of cytotoxic
drugs, hormonal & endocrine Tx
Origins in 1940s -- Goodman & Gilman
used nitrogen mustards for lymphoma
Today, >50 cytotoxic agents; >15
hormonal agents in use
Not usually used for localized cancers
Chemotherapy
Mainly used for disseminated cancers systemic at
time of diagnosis:
Cancers with metastatic spread
==> intent to prolong life, palliate symptoms
hematological malignancies
==>cure or prolong life
Cancers with suspected micrometastatic spread (
adjuvant therapy)
Tumor cell sanctuaries -- CNS & testes a
limitation
Chemotherapy
Adjuvant therapy:
debulking prior to surgery
augment effects of RT (either additive,
or as radiosensitizers)
May be used in cancer prevention
trials on estrogen receptor antagonists
for women at high risk of breast cancer
Can be administered regionally
Chemotherapy
Localized Administration
Limb: Melanoma -- isolated limb perfusion
Abdomen: Ovarian Ca -- intraperitoneal Tx
CNS: Meningeal disease -- intrathecal/ iventric.
Skin Lesions: Squamous, basal cell Ca -- topical
Liver: Hepatoma, mets -- hepatic artery infusion
Pleura: Pleural effusions -- pleural instillation
Bladder: Superficial bladder Ca -- intravesical
Cure Possible

Choriocarcinoma Embryonal
Neuroblastoma rhabdomyosarcoma
Acute leukemias Intermediate- grade
Testicular cancer lymphomas
Hodgkins disease Lymphoblastic
Wilms tumor lymphoma
Ewings sarcoma Small Burkitts lymphoma
cell lung ca.
Adjuvant Cures
Possible
Breast cancer
Colorectal cancer
Osteogenic sarcoma
Soft tissue sarcoma
Head & neck cancer
Not yet Curable
Bladder cancer Gastric cancer
Breast cancer Glioblastoma
Cervical/ endometrial multiforme
cancers Soft tissue sarcoma
Prostate cancer Colorectal cancer
Multiple myeloma Chronic leukemia
Low- grade lymphomas Head & neck ca.
Poor Response

Osteogenic sarcoma
Pancreatic cancer
Renal cell carcinoma
Thyroid cancer
Non- small cell lung cancer
Melanoma
Prinsip kemoterapi kanker
Kanker hanya terdeteksi bila jumlah sel
109,yang dapat dibasmi 99.9%, sisa 106.
Sebaiknya sel tumor kurang dari 10 5
Ada hubungan dosis respon positip, dosis
tinggi => efek tinggi => sampingan tinggi
Pemakaian intermiten, efektif tanpa
mengganggu sel normal
Prinsip kemoterapi kanker
Kemoterapi tertuju pada sel kanker
Pemakaian dini:
jumlah sel masih sedikit
sel resisten belum banyak
obat mudah mencapai semua sel kanker
keadaan umum pasien masih baik
Prinsip kemoterapi kanker
Sifat pertumbuhan sel ganas mula-mula
lambat, lalu eksponensial, kemudian
melambat kembali
Efektifitas selektif terhadap sel histologik
tertentu
Prinsip kemoterapi kanker
Terapi kombinasi:
mekanisme kerja beda
efek toksik beda
diberikan pada masa siklus yang tepat.