Barsky: Cancer Flashcards
Men have the highest incidence of which cancer?
Women have the highest incidence of which cancer?
Both men and women have the highest death rates from which cancer?
prostate; breast; lung
Two factors leading to tumor progression?
genetic: mutations, rearrangements in proto-oncogenes
epigenetics
It’s important to know that cancer is a multi-hit event. Why does this help explain why cancer is a disease of aging?
It takes years to accumulate “hits” - this is why neonates don’t get cancer
Why is it important to catch cancer when it is “in situ” vs. invasive?
To become metastatic/invasive, cancer must break through the epithelial barriers of the blood or lymph vessels and spread through the circulation. If it is still contained within its barriers, the cancer cells can be surgically removed and rid of before it spreads systemically.
**once you have invasion, it doesn’t take much to develop micrometastasis
4 properties of cancer
disease of uncontrolled growth
disease of invasion and metastasis
clonal dominance
loss of differentiation
What is clonal dominance?
cells in a cancer have come from one single ancestral cancer cell
What is tumor heterogeneity?
as tumors grow, mutant subclones are derived - as the tumor grows, it acquires other traits through tumor heterogeneity
**this makes it hard to treat cancer (too many different types of cells)
4 types of cancer therapy
surgery
radiotherapy
chemotherapy
immunotherapy
List 3 limitations in treating cancer
- lack of tumor specific antigen
- tumor cell heterogeneity
- micrometastasis
List some causes of human cancer
environmental carcinogens UV radiation ionizing radiation viruses lifestyle, diet, immune status hereditary factors or genes
How do chemical carcinogens cause cancer?
bind to DNA (electrophile) and form DNA adducts which give rise to mutations; if the mutations occur in “hot spot” genes, then they can be carcinogenic
How does UV/ionizing radiation cause cancer?
chromosome breakage, translocations and point mutations; ACTION IS SIMILAR TO CHEMICAL CARCINOGENS - FORMATION OF DNA ADDUCTS
What genes in HPV are important? What do they do?
E6 and E7; they inactivate tumor suppressors p53 and pRb
How is UV/ionizing radiation different from other chemical carcinogens?
can cause single and double stranded DNA breaks
4 cancers associated with Epstein Bar Virus?
Burkitt’s lymphoma
B cell lymphoma in AIDS pts
Hodgkin’s disease
Nasopharyngeal cancer
Why do immunodeficient hosts have a higher rate of certain cancers, esp virally-induced cancers?
they lack the proper antigen recognition of the viral cells
**immunocompromised pts not necessarily more susceptible to cancers like breast cancer that don’t have an antigenic marker
T/F: Nuns (women who are nulliparous) have a high rate of breast cancer
True
Men who are obese have a higher rate of this cancer
esophageal
Women who eat fatty foods have a higher rate of this cancer
breast
People who eat red meat have a higher incidence of this cancer
colon
Do more cancers have a familial component or inherited component?
familial
**certain cancers run in families
What is the cause of MOST cancers?
spontaneous and sporadic - UNKNOWN CAUSE
List two key properties of cancers
- growth in an uncontrolled manner
2. invasion and metastasis
Genes that code for products associated with neoplastic transformation
oncogenes
NORMAL genes that affect growth and differentiation
Protooncogenes
What activates protooncogenes to oncogenes?
point mutations
chromosomal translocation
gene amplification
T/F: Some cancers are caused by a gain of function mutation, while others are due to loss of function mutation (tumor suppresors)
True
One of the most commonly mutated genes seen in virtually all types of human cancers;
Multiple complex functions involving antiproliferation and apoptosis
p53
This syndrome is caused by one mutant p53 allele
Li Fraumeni syndrome
Certain DNA viruses can inactivate this tumor suppressor
p53
What is unique about the retinoblastoma hypothesis?
two hits - both Rb genes must be inactivated by somatic mutation, but FAMILIAL cases only require one hit
T/F: Cancer is characterized by methylation and histone deacytylation imbalance
True
Active migration of neoplastic cells out of their tissue or origin and across host tissue boundaries
cancer invastion
A secondary tumor colony discontinuous from the primary tumor
metastasis
How do sarcomas tend to spread?
Through the blood vessels
How do carcinomas tend to spread?
Through the lymph
3 routes of metastasis
blood
lymph
transcoelomic (seeding by body cavities) *Peritoneal, pleural, pericardial and subarachnoid spaces
Grading is measure of the degree of differentiation. What are the categories of GRADING?
1-4; well differentiated - moderately - poorly differentiated - undifferentiated
Grading of cancer tells us about (blank)
prognosis
Staging is a degree of invasion and metastasis. What system is used for staging?
T: tumor size (ex: T1, T2, T3…)
N: nodes (how many nodes involved ex: N0, N1…)
M: metastasis present or no
Compare grading and staging
grading: differentiation
staging: invasion and metastasis
grading: 1-4
staging: TNM
What happens to tumor cells when they become carcinogenic?
they become less cohesive and lose their attachment to matrix components (more motility); they degrade the ECM via metalloproteinases and migrate
What is the soil seed hypothesis of paget?
cancers tend to grow in certain organs
Is systemic metastasis an early event?
yes, circulating tumor cells are found in the blood early on in cancer; disseminated cells are found in organs early, too
Why do many cancers recur?
cancer stem cells
3 properties of all stem cells
self-renewal
symmetrical and asymmetrical cell division
pluripotent
Propeties of cancer stem cells
Exist in a resting or dormant state
Resist chemotherapy and radiotherapy
Express embryonic stem cell pathways
Replenish the dividing cell population of the tumor
What must be present in order for metastases to occur?
cancer stem cells
Why might tumor recurrence occur?
stem cells are repopulating the tumor
**tumor treatments need to not only target tumor cells, but stem cells as well
Any gene or gene product altered in tumor progression
tumor marker
weight loss, weakness, anorexia, and anemia associated with cancers
cachexia
Can tumor markers be used for definitive diagnosis?
no; but can be used for staging, detecting recurrences, and monitoring effectiveness and therapy
GIVE US INFORMATION ABOUT PROGNOSIS: DISEASE-FREE SURVIVAL, OVERALL SURVIVAL, LENGTH OF LATENCY
prognostic markers
What are some examples of prognostic markers?
ER (estrogen receptor) in breast cancer; p21 and p27 in prostate cancer
GIVE US INFORMATION REGARDING THE EFFECTIVENESS OF A CHEMOPREVENTIVE OR THERAPEUTIC STRATEGY BEFORE DIRECT TUMORAL MEASUREMENTS CAN BE ASSESSED.
surrogate end point markers (intermediate markers)
**used in clinical trials as a marker or how effective treatments are
Why do we need predictive markers?
to guide therapy
