Anti-Neoplastics #2 Flashcards
Vaccination and carcinoma development link.
Which chemical compounds exist in our environment that can cause cancer?
Asbestos, cadmium, vinyl chloride, benzene, uranium, nickel
How does age increase your risk of developing cancer?
▪ Weakening of immune system
▪ The longer exposure to environmental carcinogens
Prostate cancer and diet in humans
Better care of your diet = decreased risk
Cancer is a genetic disease. What does that mean?
One or several genes re mutated, wrong amount of genetic material, or abnormal genetic material.
Most cancers are, in 90% cases, are ?
Sporadic.
▪ Accumulation of mutations in somatic cells over a lifetime
▪ Develop at older age, in certain cells in the body – not every cell
Hereditary cancer occurs in what % of cases? Define this.
less common, 5-10% cases)
▪ Inherited susceptibility through germ-line mutation (passed down from mother or father). Why? At birth you have this mutation and…
▪ Gives tumor a “head start’
▪ This is why some cancers develop at younger age. Does not mean that cancer at younger age can’t be somatic.
What % of cancer cases are random errors?
( ~ 66% cases)
▪ Environmental factors play a large role in multiplying these errors
This is why it’s important for the DNA damage and response pathway to be intact. If there is a mutation in this response pathway, cancer can occur.
What is important to understand in order to treat cancer?
Understanding what type of a mutation a patient has might affect how their cancer is treated. The point is to try and find a mutation that’s driving the tumor to inhibit the pathway and to slow down or stop the growth of the tumor.
Genes with Mutations Linked to Hereditary Cancer Risk - breast cancer in women
BRCA 1, 2, TP53
Genes with Mutations Linked to Hereditary Cancer Risk - breast cancer in men
Genes with Mutations Linked to Hereditary Cancer Risk - colorectal cancer
TP53
BRCA1 and 2 are responsible for?
Genome stability
Gene mutation can be inherited from?
Either mother or father. RARELY both. If both –> embryo won’t develop.
Genes with Mutations Linked to Hereditary Cancer Risk - endometrial cancer
Genes with Mutations Linked to Hereditary Cancer Risk - Fallopian tube, ovarian, primary peritoneal cancer
see below
Genes with Mutations Linked to Hereditary Cancer Risk - gastric cancer
Genes with Mutations Linked to Hereditary Cancer Risk - Melanoma
Define somatic alteration.
In some situations, abnormal copy can be lost or changed during lifetime due to other circumstances. This change is called somatic alteration.
Genes with Mutations Linked to Hereditary Cancer Risk - Pancreatic cancer
BRCA1, 2, TP53
Genes with Mutations Linked to Hereditary Cancer Risk - Prostate cancer
Look at p10 and tp53 as well
What dog breed am I?
What types of cancer am I more at risk of developing?
What dog breed am I?
What types of cancer am I more at risk of developing?
What dog breed am I?
What types of cancer am I more at risk of developing?
What dog breed am I?
What types of cancer am I more at risk of developing?
Which dog breed is the most at risk of developing cancer?
Golden retrievers - at as young as 6 years of age.
Female goldens = 66%
Male goldens = 60%
General dog population cancer risk?
14-27%
What cat breed am I?
What types of cancer am I more at risk of developing?
How were cancers categorized in the past?
Cancers were categorized in terms of their tissues of origin and their stages in clinical progression. For more than half of century, histopathology was the major
tool in the clinical oncology.
1-2 = ok stage
3-4 = associated with metastasis
4 = death sentence
Why are therapy success rates so low?
There are distinct subcategories within one disease: this explains low overall therapy success rates over the past three decades
Increasing role of molecular diagnosis in the development and clinical introduction of novel therapeutics
Depending on molecular signature, they will respond to certain drugs/drug combos.
Small-molecule therapeutics and their intracellular targets that have been identified through research on the signaling pathways within cancer cells are the basis for targeted therapies
Why is the immune system not attacking cancer?
Manipulate with therapeutic drugs to tell immune system to wake the fuck up and fight back!
What are the molecular bases of cancer?
- Cellular functions are controlled by proteins, which are encoded by DNA organized into genes.
- Cancer is cell growth disease where cells undergo division many more times than normal. This makes the cells prone to replication errors accumulating mutations, which are not repaired
When looking at a normal cell, growth factors results in?
When looking at a normal cell, death signals results in?
Cell proliferation
Controlled cell death (apoptosis)
These two processes strike a balance = homeostasis.
How do normal cells become cancerous?
Uncontrolled situation aka when proliferation and no growth inhibition signals are provided, no apoptosis occurs = normal cells proliferating and then if not die then they are considered neoplastic aka cancer like cells.
What disrupts normal tissue homeostasis
Some oncogenes are over-expressed in certain types of cancer. Tumor suppressors, such as p53 and p10, are imbalanced/mutated/not expressed so they can not suppress the tumor.
List the cell cycle and checkpoints.
Cell cycle is req. or growth and division.
Every cell can not divide if they don’t replicate its genome and then separate duplicated genome. Cells must perform DNA synthesis and mitosis to achieve this. Cell cycle is ordered and regulated.
G1 = req. for cell growth and DNA synthesis
S = DNA replicated
G2 = needed for cell growth and preparation for mitosis
M = mitosis and cells duplicate chromosome.
Checkpoints monitor process. If there is something wrong with checkpoints = potential for cancer
What are cell cycle checkpoints?
Cell cycle checkpoints are control mechanisms that ensure proper division of the cell
▪ Network of proteins form the DNA damage checkpoints (cyclins and cyclin dependent
kinases (Cdks)
▪ Network of proteins form DNA replication checkpoints
DNA damage can occur in proliferating cells, such as blood, colon, GI, cancer cells, and non-dividing cells such as neurons, cancers occur primarily in proliferative tissues. If not repaired, due to inappropriate expression of DNA repair genes –> damages can accumulate –> premature aging.
Epigenetics plays a huge role in cancer as well. (DNA mutation and acetylation, non-coding RNAs).
What is the central dogma of molecular bio?
Before a cell can divide, what must happen?
Each new DNA molecule will consist of?
the DNA in the nucleus of the cell must be duplicated
one old stand, and a new complimentary strand
Helicases are involved in ?
unzipping of the double stranded DNA
DNA polymerase adds ?
complementary
nucleotides
Therapeutic drugs attack?
Enzymes involved in DNA replication process
What are topoisomerases?
What is the function of Topoisomerase I and II?
Topoisomerases are enzymes that participate in the overwinding or underwinding of DNA
(act on the topology of DNA). Some drugs can inhibit topoisomerases. These drugs will inhibit proliferation of cancer cells. There are side effects associated.
Topoisomerase I: cutting and re-ligating single DNA strand of double helix
Topoisomerase II: cutting both strands of DNA double helix
Chemotherapeutic drugs cause DNA Damage. What does that mean?
Our goal is to damage DNA in cancer cells so they can not replicate and stop tumor from growing. There are many types of DNA damage. DNA response system is not happening in cancer cells. Most DNA damage gets repaired right away by special repair proteins. If DNA damage occurs in gene that makes these repair proteins, a cell has no ability to do this? –> deficiency in repairing damaged DNA which is what causes cancer.
Implications for therapy: If cancer is composed of cels deficient in DNNA repair, it is vulnerable to cells that cause DNA damage. DNA repair proteins are inhibited so can not repair damage caused by the drug.
What are the major forms of DNA damage?
Single strand or double strand break, mismatch, damaged DNA base, interstrand crosslink, intrastrand crosslink, others. These are major DNA damage situations.
BRCA1 and 2 promote?
BRCA1 & 2 promote efficient and precise
repair of mis-match and double-stranded breaks
What are the challenges that come with anti-cancer
) develop new targeted and tailored (personalized) therapies
2) chemoprevention
3) combination therapies with synergistic efficacy and minimum
toxicity
What are the different forms of anti-cancer therapy?
❖ Chemotherapy (cytotoxic, DNA)
❖ Targeted Therapy (monoclonal antibody, small molecules)
❖ Endocrine therapy (ER, AR, hormones)
❖ Immune Therapy (activation of immune system against cancer)
❖ Epigenetic Therapy (DNA methylation, histone acetylation)
❖ Chemoprevention (dietary products and supplementation )
How many drugs are used to treat cancer?
More than 100 chemo drugs are used to treat cancer – either
alone or in combination with other drugs
How did chemo drugs differ?
Chemo drugs are different in their chemical structures, how they
are taken, their specificity in treating particular cancer type, and
their side effects
Are chemo drugs capable of distinguishing between cancerous cells and non-cancerous cells?
Chemo drugs cannot distinguish between cancer cells and
normal cells: cause of adverse effects
How are chemo drugs classified?
Chemo drugs can be classified by how they work, their chemical
structure, and their relationship to other drugs
Why is it important to understand how chemo drugs work?
Knowing how the drug works is important in predicting side
effects from it, in making decision about combination of drugs,
and in planning exactly when each drug should be given, in
which order and how often
