10. Biology of Cancer Flashcards
6 characteristics of benign tumors
- grow slowly - well-defined capsule - non invasive (don’t grow past capsule) - well differentiated (similar to original cells) - low mitotic index - don’t metastasize
6 characteristics of malignant tumors
- grow rapidly - not encapsulated - invasive - poorly differentiated (anaplasia) - high mitotic index - can spread distantly (metastasize)
malignant epithelial tumors
carcinomas
malignant connective tissue tumors
sarcomas
marked variability of size and shape
pleomorphic (malignant tumors)
lymphatic tissue cancers
lymphomas
cancers of blood-forming cells
leukemias
pre-invasive epithelial malignant tumors of glandular or epithelial origin that have not broken through the basement membrane or invaded surrounding stroma
carcinoma in situ (CIS
type of CIS that occurs in the breast
ductal carcinoma in situ (DCIS)
3 fates of CIS
- remain stable for long time - progress to invasive and metastatic cancers - regress and disappear
What type of benign tumor does cause problems?
brain tumors -> limited space to grow so will affect the functions of surrounding tissues
primary vs secondary sites
- primary site: where cancer started - secondary site: where cancer spread (metastatic site)
biologic markers produced by cancers cells or found on plasma cell membranes in the blood, CSF, or urine
tumor markers
2 types of tumor markers
hormones and antigens
increase in catecholamines indicates what?
adrenal medullary tumor (ex. pheochromocytoma)
increase in ACTH indicates what?
adrenal, pituitary, or hypothalamic tumors
increase in b-HCG indicates what?
germ cell and hepatic cancers
3 ways tumor markers are used
- screen and identify individuals at high risk for cancer - help dx specific type of tumor in pts w/ clinical manifestations - follow the clinical course of a tumor
increase in carcinoembryonic antigen (CEA) indicates what?
colon, lung, pancreas, or breast cancer
alpha fetoprotein (AFP) is used to monitor what types of cancers?
hepatic and germ cell (testicular and ovarian)
CA-125 is used to monitor what type of cancer?
ovarian
What problem has been found with prostate specific antigen (PSA)?
many false positives -> approximately 75% of men w/ increased PSA don’t have prostate cancer on biopsy
cancer is mainly a disease of what?
aging
as a result of mutation, a cell acquires characteristics that allow it to have a selective advantage over it neighbors (increased growth rate/decreased apoptosis)
clonal proliferation or expansion
T/F: cancer can occur from a single mutation
False; multiple mutations are required before cancer can develop
4 types of gene mutations related to cancer
- secretion of growth factors - increased GF receptors - signal on cell-surface receptor is mutated in the “on” position - Intracellular signaling protein to promote replication
genes that regulate normal cellular proliferation
proto-oncogenes
mutation gained in proto-oncogene so that it can’t slow down
oncogene
genes that normally inhibit the cell cycle and proliferation
tumor-suppressor genes
the “guardian of the genome” - signal to undergo apoptosis
p53
Explain how cancer causing genes can transmit from one generation to the next
- inactivation of tumor-suppressor genes requires 2 mutations (1 per allele) - single germ-cell mutation transmits a mutation to the child (inherited) - only requires 1 somatic cell mutation to completely inactivate tumor-suppressor genes
How do cancers participate in angiogenesis
secrete angiogenic factors such as vascular endothelial growth factor (VEGF)
drug that inhibits VEGF
Avastan
protective caps on end of each chromosome that become smaller w/ each division
telomeres
what is used to place and maintain telomeres
telomerase
Explain how cancer cells use telomeres to become immortal
cancer cells can secrete telomerase to restore and maintain telomeres -> allow for continuous division without stop
List the 6 hallmarks of cancer
- Self-sufficiency (in growth signals) - Evading growth suppressors - Tissue invasion and metastasis - Replication immortality - Induce angiogenesis - Resist cell death (apoptosis
genes tested for breast cancer
BRCA1/BRCA2
hereditary nonpolyposis colorectal cancer (no polyps present -> requires regular screenings)
Lynch syndrome
familial adenomatous polyposis is cancer of the colon/rectum caused by mutations in what gene?
APC
gene associated w/ thyroid cancer
RET
gene associated w/ retinoblastoma
RB1
benefits of genetic testing (4)
- possible relief in knowing - fewer checkups - informed decisions - interventions can be made
limitations of genetic testing (3)
mutation may be present but: - may be acquired, not inherited - may never lead to disease - may go undetected
T/F: most cancer is inherited
False: most is NOT inherited
encode for proteins that are involved in repairing damaged DNA
caretaker genes
Ex. of caretaker gene
p53
KSHV
kaposi’s sacroma herpesvirus
HTLV
human t cell leukemia-lymphoma virus (retrovirus)
chronic infections w/ H. pylori are associated w/ what?
- PUD - stomach carcinoma (most stomach cancers) - MALT lymphomas
3 ways tumors spread
- direct invasion (local spread) - metastasis (via lymphatics and blood) - metastasis through implantation (accidentally during procedures)
Describe the steps of direct invasion (8)
- tumor attaches to other cell - degrade matrix using enzymes - locomotion of tumor cell into matrix (invadopodia) - cellular multiplication/growth - mechanical pressure - release of lytic enzymes - decreased cell-to-cell adhesion - increased motility
entry of tumor cells into circulation
intravasation
exit of tumor cells from circulation
extravasion
Describe the steps of metastasis (5)
- direct/continuous extension - penetration into lymphatics, blood vessels, or body cavities - transport into lymph/blood - arrive at secondary site - entry and growth
where does metastasis often occur first
in the first capillary bed encountered by circulating tumor cells
preferential growth of cancer cells in certain organs
organ tropism
Most common metastasis sites
brain, bone, liver, and lung
TNM staging
- Tumor: # equals size of tumor and local extent - Node: higher # means more nodes involved - Metastasis: # indicates extent of metastasis
increase in ____ comes from mutations of proto-oncogenes -> oncogenes
pro-growth signals
decrease in ____ comes from mutations in tumor-suppressor genes
anti-growth signals
cancer cell develops ability to secrete GF that stimulate itself for cellular replication
autocrine stimulation
What happens if there is an increased number of GF receptors?
the cell will replicate in response to very low levels of GF
examples of oncogenes
- c-ras - myc - fos - jun
most common genetic defects found in human cancers
mutations of tumor-suppressor genes
when both tumor-suppressor gene alleles become mutated
loss of heterozygosity
What is another way to lose heterozygosity of tumor-suppressor genes other than mutation
alleles become hypermethylated (gene silencing)
How is a PET scan used to find cancer metastases?
able to locate metastases that are using up more glucose than normal cells (up-regulated glucose transport)
What triggers the extrinsic pathway of apoptosis?
Fas - “death receptor”
What is one of the most important activators of the Fas receptor
TNF-a
What influences pain in cancer?
- fear/anxiety - sleep loss/fatigue - overall physical deterioration
T/F: pain is one of the first signs of cancer
False; little/no pain is associated w/ early stage of cancer
What is the most frequently reported symptom of cancer and cancer treatment?
fatigue
most severe form of malnutrition that is present in 80% of cancer pts at death
cachexia
What is included in cachexia (5)?
- anorexia - early satiety - weight loss - taste alternation - altered metabolism
Causes of anemia in cancer (4)?
- chronic bleeding due to iron deficiency - severe malnutrition - medical therapies (chemo) - malignancy in blood forming organs
Causes of leukopenia and thrombocytopenia in cancer?
- direct tumor invasion to the bone marrow - chemo drugs are toxic to the bone marrow
symptom complexes triggered by cancer but not caused by direct local effects of the tumor; commonly due to biologic substances released from the tumor or by immune responses triggered by the tumor
paraneoplastic syndrome
in what cancers are paraneoplastic syndromes most often seen?
breast, lung, and ovarian cancer
What system is most affected by paraneoplastic syndromes?
nervous system (can cause various neurological disorders that precede other cancer symptoms)
obstruction of blood flow through the SVC
superior vena cava syndrome
What type of cancer is most common w/ SVC syndrome
adenocarcinoma of the right lung
Most common symptom of SVC syndrome
dyspnea
Other major symptoms of SVC syndrome
cough, chest pain, headache, head fullness, and facial swelling
single-agent vs combination chemotherapy
- single agent: usually shrinks cancer but rare provides cure - combination: attacks cancer from several weak points at the same time (limits dose and toxicity of drugs)
chemo given before localized (surgical or radiation) treatment of cancer -> seeks to shrink tumor so that surgery many spare more normal tissue
neoadjuvant chemotherapy
chemo given after surgery with the goal of eliminating micrometastasis
adjuvant chemotherapy
chemo that seeks to cause shrinkage and disappearance of tumors
induction chemotherapy
targeted method used to kill cancer without excessive toxicity and avoid damage to normal structures
ionizing radiation
How does ionizing radiation destroy cancer?
damages cancer cell’s DNA
the first lymph node to which cancer cells are most likely to spread from a primary tumor
sentinel node
4 tissue types affected by cancer treatment
mainly includes labile cells (continuous replication) - GI tract - bone marrow - hair and skin - reproductive tract
