Lecture 7 - Anticancer Meds Flashcards
Cancer
also known as a malignant tumor or malignant neoplasm, is a group of diseases involving abnormal cell growth with the potential to invade or to spread to other parts of the body
____ have a higher chance of getting cancer and a higher chance of dying earlier
men
List the 3 top cancers for men and women in Canada
Men:
1) Prostate
2) Colorectal
3) Lung
Women:
1) Breast
2) Lung
3) Colorectal
Cancer is primarily a disease of ____ age
old
Malignant
if tumor invades surrounding tissue (cancerous)
Benign
if tumor has no effect on surrounding tissue (non-cancerous)
Metastatic
if individual cells break away and start a new tumor elsewhere (cancerous)
Describe the path to cancer
-Clonal proliferation
-Starts from a single cell
-Expansion in steps
-Pre-malignant states
(Polyp, MDS, MGUS)
-Serial accumulation of mutations
(Clonal evolution, resistance)
List some hallmarks of cancer
- Self sufficiency in growth signals
- Insensitivity to anti-growth signals
- Evading apoptosis
- Limitless reproductive potential
- Sustained angiogenesis
- Tissue invasion and metastases
- Genomic instability
Is cancer a genetic disease?
Yes
Cancer arises from the accumulation of _____ changes (somatic mutations)
*Genetic selection at the level of single cells
genetic
Most cancers incur a minimum of ______ different gene mutations
5 (6-9)
We don’t inherit cancer but we do inherit _______ to cancer
dispositions (susceptibility)
_______ is a hallmark of cancer cells
Aneuploidy
What is aneuploidy?
The presence of an abnormal number of chromosomes in a cell
2 components of Etiology of cancer
Nature:
-What we inherit
Nurture
-Environmental factor (what we do to our body) ex. smoking, UV radiation, etc.
You need an _____ and an elongated promoter to lead to cancer
initiator
Tumor initiators = ______
mutagens
Tumor Promoters = _____ ______
proliferation inducers
List some tumor initiators (mutagens)
- X rays
- UV light
- DNA alkylating agents
List some tumor promoters (proliferation inducers)
- Phorbol esters
- Inflammation
- Alcohol
- Estrogens and Androgens
- Epstein-Barr Virus
Cell cycle phases:
G1 (gap phase)
the cell grows and prepares to synthesize DNA
Cell cycle phases:
S (synthesis phase)
in which the cell synthesizes DNA
Cell cycle phases:
G2 (second gap phase)
in which the cell prepares to divide
Cell cycle phases:
M (mitosis phase)
cell division occurs
Cell cycle phases:
G0 (arrest/quiescent)
cell is in resting state
Cell cycle phases:
Checkpoint 1
G1/S checkpoint:
Cell monitors size and DNA integrity
Cell cycle phases:
Checkpoint 2
G2/M checkpoint:
Cell monitors DNA synthesis and damage
Cell cycle phases:
Checkpoint 3
M checkpoint:
Cell monitors spindle formation and attachment to kinetochores
What protein complexes are involved in the cell cycle?
- Cyclins
- Cyclin dependent kinases (Cdks)
Are Cdk (cyclin dependent kinases) levels stable?
yes
Are cyclin levels stable?
no they change throughout the cell cycle
The ability to drive through the checkpoint are reliant on ??
cyclins and cdks (oncogenes)
*cdk = cyclin dependent kinase
Cdks must bind to the correct ___ in order to function
cyclin
What do kinases do?
enzymes that add phosphate groups to proteins to convert them from an “off” to an “on” state
Describe the pathogenesis of cancer:
_____ are activated
___ ______ ____ are inactivated
Oncogenes are activated
Tumor suppressor genes are inactivated
Oncogene = ?
gas pedal
Tumor suppressor genes = ?
brakes
What is p53?
a class tumor suppressor
What is Rb?
also a classic tumor suppressor
Rb binds to a protein called ____
E2F1
*when bound to Rb, E2F1 can’t function
_______ = drives cell cycle forward and bypasses checkpoints
Oncogenes
______ = an amplified oncogene
HER2/neu
*a growth factor receptor
25-30% of ____ cancers over-express HER2/neu
breast
____ is used as a treatment for breast cancers that over-express HER2/neu
Herceptin
___ = a frequently mutated oncogene
Ras
Translocations can be ? (2)
- Balanced
- Reciprocal
Aneuploidy can be ? (4)
- Pseudodiploid
- Hyperdiploid
- Complex
- Random loss or gain
- Loss of tumor suppressor function
- Proto-oncogenic gain of function (into oncogene)
What is the Philadelphia chromosome?
- Translocation between chromosome 22 and chromosome 9
- Classic oncogenic rearrangement associated with a variety of leukemias
- BCR-ABL tyrosine kinase fusion
- Imatinib (Gleevec) is an Abl-kinase targeted tyrosine kinase inhibitor (TKi) used in the treatment of the Ph+ CML and other tumors
When is chemotherapy most effective?
when growth fraction is high
Describe early stages of tumour growth?
- high growth fraction
- short doubling times
Describe late stages of tumour growth?
- low growth fraction
- long doubling times
Benign = ?
non-cancerous
“polyp”
Malignant = ?
cancerous
Malignant epithelial = ?
carcinoma
Malignant mesenchyme = ?
sarcoma
Malignant hematopoietic = ?
leukemia, lymphoma, myeloma
Hyperplasia
increased number of cells
Hypertrophy
increased size of cells
Dysplasia
disorderly proliferation
Neoplasia
abnormal new growth
Anaplasia
lack of differentiation
Tumor
originally meant any swelling, but now equated with neoplasia (abnormal new growth)