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CANC380 > Module 06 - Cancer Therapies > Flashcards

Module 06 - Cancer Therapies Flashcards

1
Q

What are the 3 main types of cancer therapies?

A

1- localized
2- Systemic
3- targeted

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2
Q

What is localized therapy?

A

Treatment that affects cells in the tumour and surrounding area

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3
Q

What is systemic therapy?

A

Treatment that uses substances that travel through the bloodstream to reach and affect cells all over the body

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4
Q

What is target therapy?

A

Treatment that uses drugs or other substances to block cancer progression by interfering with specific molecules

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5
Q

Give 4 examples of localized therapy

A

1- Surgery
2- External Beam Radiation
3- Brachytherapy
4- Photodynamic therapy

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6
Q

What are some uses of surgery in cancer therapy?

A
  • Mainly to remove cancerous tissue
  • Can be used with other therapies such as chemo or radiation
  • Can be used to diagnose and stage cancer
  • Preventive, or prophylactic surgery, to prevent or lower the risk of developing certain type of cancer
  • can be used to relieve symptoms
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7
Q

Describe external beam radiation therapy

A

Works by damaging a cancer cell’s DNA
can treat larger areas of the body or more than one area, such as the tumour and nearby lymph node
- can consist of x-rays, gamma rays, or electron, proton and neutron particles

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8
Q

Describe brachytherapy

A

radioactive isotope is place directly into or very close to the tumour, or where the tumour was surgically removed
- can treat cancer with a larger dose of radiation than can be given with external beam radiation therapy

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9
Q

Describe photodynamic therapy

A

Destroys cancer cells by using a drug called a photosensitizer

  • Used to treat tumours in the lining of some organs and to relieve blockages caused by tumours in the esophagus or lungs
  • The photosensitizer is given and is absorbed and stays in the cancer cells longer than in normal cells
  • cancer cells are then exposer to low intensity laser light: the photosensitizer absorb the light and a chemical reaction occurs that kills the cancer cells while sparing most normal cells
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10
Q

What are the 3 goals of systemic cancer therapies?

A
  • Control cancer while minimizing the side effects of treatment as much as possible
  • Slow the growth of cancer, killing cancer cells that may have spread to other parts of the body and stop the spread of cancer
  • Relieve symptoms of cancer, such as pain
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11
Q

Give 4 examples of systemic therapy

A

1- Conventional chemotherapy
2- Hormone therapy
3- Biological therapy/immunotherapy
4- Systemic radiation

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12
Q

How does conventional chemotherapy work and give an example

A

Kill all cells that are actively dividing

Ex: use of cytotoxic drugs doxorubicin and docetaxel

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13
Q

How does hormone therapy work and give an example?

A

Inhibits hormone-induced tumour growth by manipulating homeostatic control pathways
Ex:
- tamoxifen blocks estrogen in breast cancer
- Finasteride blocks testosterone in men with prostate cancer

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14
Q

How does biological therapy/immunotherapy work and give an example?

A

Immunotherapy enhances the immune system’s ability to target cancer cells; forms may include the use of antibodies or drugs to target specific aspects of tumours cell biology
Ex: PD-L1 immune checkpoint blockade therapy

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15
Q

How does systemic radiation work ?

A

Uses radioactive materials that travel throughout the bloodstream to treat certain types of cancer such as thyroid cancer, or to relieve pain when cancer has metastasized to bone

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16
Q

Where did chemotherapy origin?

A

In chemical warfare.
In 1943 during World War 2, a US ship carrying nitrogen mustard gas was bombed in an italian harbour. Many soldiers died and the resulting autopsies showed taht several cell lines in bone marrow were completely eliminated.
This was seen as a possible treatment for types of leukemia

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17
Q

What are the contributions of Louis Goodman and Alfred Gilman to the history of chemotherapy?

A

Use of nitrogen mustard to treat a patient with non-hodgkin’s lymphoma and demonstrate for the first time that chemotherapy can induce tumours regression

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18
Q

What are the contributions of Sydney Farber to the history of chemotherapy?

A

used Antifolates to successfully induce remissions in children with acute lymphoblastic leukemia (ALL)

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19
Q

What are the contributions of George Hitchings and Gertrude Elion to the history of chemotherapy?

A

Synthesize the purine analogue 6-mercaptopurine

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20
Q

What happened in 1955 that was significant for the history of chemotherapy?

A

The National Chemotherapy program begins at the National Cancer Institute; a systemic program for drug screening commences

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21
Q

What are the contributions of Roy Hertz and Min Chiu Li to the history of chemotherapy?

A

Demonstrated that methotrexate as a single agent can cure choriocarcinoma, the first solid tumour to be cured by chemotherapy

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22
Q

What happened in 1959 that was significant for the history of chemotherapy

A

FDA approves the alkylating agent cyclophosphamide

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23
Q

What happened in 1965 that was significant for the history of chemotherapy?

A

Combination chemotherapy (POMP regimen) is able to induce long-term remissions in children with Acute Lymphoblastic Leukemia

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24
Q

What are the contributions of Vincent DeVita to the history of chemotherapy?

A

cure lymphomas with combination therapy

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25
Q

What are the contributions of Emil Frey to the history of chemotherapy?

A

demonstrated that chemotherapy given after surgical removal of osteosarcoma can improve cure rates (adjuvant chemo)

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26
Q

What happened in 1975 that was significant to the history of chemo?

A

A combination of cyclophosphamide, methotrexate, and fluorouacil CMF was shown to be effective as adjuvant treatment for node-positive breast cancer

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27
Q

What happened in 1978 that was significant to the history of chemotherapy?

A

FDS approves cisplatin for the treatment of ovarian cancer, a drug that would prove to have activity across a broad range of solid tumours

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28
Q

What happened in 1989 that was significant to the history of chemo?

A

NCI introduces disease oriented screening using 60 cell lines derived from different types of human tumours

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29
Q

What happened in 1992 that was significant to the history of chemo?

A

the FDA approves paclitaxel (Taxol) which becomes the first blockbuster oncology drug

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30
Q

What was the first “blockbuster” oncology drug?

A

Paclitaxel (taxol) approved in 1992

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31
Q

What are the contributions of Brian Druker to the history of chemotherapy?

A

His studies led to FDA approval of imatinib mesylate (Glivec) for chronic myelogenous leukemia, a new paradigm for targeted therapy in oncology

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32
Q

What are 2 significant events in the history of chemo that happened in 2004?

A

1- FDA approves bevacizumab (avastin), the first clinically proven anti-angiogenic agent, for the treatment of colon cancer
2- Harvard researchers define mutations in the epidermal growth factor receptor that confer selective responsiveness to the targeted agent gefitinib, indicating that molecular testing might be able to prospectively identify subsets of patients that will respond to targeted agents

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33
Q

What are 3 types of chemotherapeutic agents?

A

1- alkylating agents
2- anti-metabolites
3-plant-derived chemotherapies

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34
Q

What is the mechanism of alkylating agents chemotherapy?

A

Bind to DNA to prevent its replication

Ex: nitrogen mustard forms covalent bond with DNA

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35
Q

What are 2 commonly use alkylating agents?

A

cyclophosphamide and chlorambucil

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36
Q

describe the mechanism of nitrogen mustard

A

The alkylating intermediate of nitrogen mustard reacts with electron-donating sites on proteins and, specifically, the guanine base of DNA. Crosslinking occurs leading to breaks in the DNA strand, resulting in apoptosis

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37
Q

What is the mechanism of methotrexate?

A

1- MTX enters the cell by active transport by reduced folate transport (RFT-1)
2- upon entering, MTX is polyglutamated
3- MTX inhibits dihydrofolate reductase (DHFR) which converts dihydrofolate to tetrathydrofolate. tetrathydrofolate is necessary to purine synthesis
4- Reduced stores of tetrahydrofolate in decreased synthesis of thymidylate (TMP) which inhibits DNA synthesis

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38
Q

what is the general mechanism of Anti-metabolites?

A

Molecules that inhibit the use of a compound (metabolite) required for normal metabolism

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39
Q

What is the general mechanism of anti-folates

A

anti-metabolites therapy that interfere with folic acid metabolism and, consequently, nucleic acid synthesis

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40
Q

What type of therapy is methotrexate?

A

anti-folate (anti-metabolite)

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41
Q

What is methotrexate used for?

A

breast, ovarian, and bladder cancer as as a choriocarcinoma (a tumour of the placenta that arises during fetal development)

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42
Q

What are some mechanisms of resistance to anti-folate therapy?

A
  • Mutations in RFT-1 can result in reduced entry of MTX into the cell
  • Amplification of DHFR can overcome the inhibitory effect of MTX on the enzyme
  • Loss of polyglutamation on MTX reduces its inhibitory effects on DHFR, andthus can reduce the efficacy of MTC
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43
Q

What are 2 examples of plant-derived chemotherapies?

A

Taxanes and camptothecins

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44
Q

What kind of plant-derive chemotherapy is paclitaxel

A

Taxane

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45
Q

What is the mechanism of action of paclitaxel?

A

Microtubule-stabilizing agent initially extracted from the bark of the pacific Yew tree

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46
Q

What is the mechanisms of camptothecin

A

A topoisomerase inhibitor that prevents the unwinding of DNA strands, thus blocking DNA replication
It was derived from Camptotheca Acuminata, a tree native to China

47
Q

When is hormonal therapy used?

A

Control progressive or metastatic disease and is often combined with otehr therapies

48
Q

What is the mechanisms of action of hormonal therapy?

A

Either lowers hormone levels or stop hormone from acting on cancer cells
3 ways to decrease hormone levels:
- Removal of the gland or organ that makes the hormone
- Treatment of the gland or organ with radiation to destroy hormone-producting cells
- Treatment with hormones or other drugs that interfere with or stop the production of the hormone

49
Q

Give 2 examples of hormonal therapy

A

1- In breast cancer, tamoxifen blocks the estrogen receptor in cancer cells to prevent estrogen from acton on cancer cells. For this to work, tumour cells must express estrogen receptor
2- Aromatase inhibitors are drugs that stop estrogen production and have been approved to treat both early and advanced breast cancer

50
Q

What is Charles Huggins contribution to cancer therapies?

A

He received a Nobel Prize in Physiology or Medicine in 1966 for his work on hormonal control of cancer, particularly prostate cancer

  • 1940s - He found he could slow the growth of prostate cancer by blocking the action of testosterone with doses of estrogen
  • 1951 - showed that breast cancers are also dependent on specific hormones. By removing the ovaries and adrenal glands, which are sources of estrogen, he supported tumour regression in some of his patients
51
Q

What are 2 ways hormonal therapy can treat prostate cancer&

A

1- lower androgens

2- block androgens

52
Q

What are some ways hormonal therapy can lower androgens? (3)

A
  • Surgical castration
  • Luteinizing hormone-releasing hormone (LHRH) agonists or LHRH antagonist can both be administered to lower the amount of testosterone made by testes, although mechanism of action are slightly different
  • Inhibition of the enzyme CYP17 blocks androgen production by cells, including prostate cancer cells
53
Q

What are some ways hormonal therapy can block androgens? (3)

A
  • Androgen-receptor blockers (anti-androgens) compete with androgens for binding to the androgen receptor (ex: flutamide, bicalutamide)
  • A newer type of anti-androgen is enzalutamide, which acts by blocking androgen signalling in cancer cells after androgens have interacted with the androgen receptor
54
Q

What is the general mechanism of targeted therapies?

A

Block the growth and spread of cancer by interfering with specific molecules involved in the growth, progression, and spread of cancer
Growth factors, signalling molecules, apoptosis modulators, and angiogenesis-associated molecules have become targets for cancer therapy

55
Q

What are 4 examples of targeted therapy?

A

1- imatinib
2- Bevacizumab
3- Gefitinib
4- Herceptin

56
Q

What is the mechanism of Imatinib?

A

Inhibits the oncoprotein BRC-ABL kinase in chronic myeloid leukemia

57
Q

What is one limitation of Imatinib

A

problems with drug resistance have occurred

58
Q

What is the mechanism of Bevacizumab?

A

Anti-vascular endothelial growth factor (VEGF) antibody used in renal-cell carcinoma; VEGF is a growth factor that stimulates formation of new vessels in the tumour environment to allow increased delivery of nutrients and, thus, tumour cell proliferation

59
Q

What is the mechanism of Gefitinib?

A

Epidermal growth factor receptor (EGFR) inhibitor that binds the ATP-binding function of the tyrosine kinase in non-small cell lung carcinoma; limited success of the drug in larger clinical trials

60
Q

What is the mechanism of herceptin?

A

A monoclonal antibody that targets the HER2 receptors in breast cancer; the HER2 gene is amplified in some breast cancers resulting in overexpression of epidermal growth factor and, thus, uncontrolled cell proliferation

61
Q

What are 6 ways angiogenesis can be inhibited?

A

1- Preventing activation of macrophages or endothelial cells by tumours cells (tumour cells can induce these cells to over-express angiogenic factors)
2- Preventing or decreasing the secretion of angiogenic factors by tumour cells OR increasing the secretion of anti-angiogenic factors
3- Targeting the actions of VEGF (because most solid tumours overexpress VEGF)
4- Inhibiting the proteases that degrade the ECM such that endothelial cells ahve room to proliferate and spread to form new vessels
5- Inhibit endothelial cell proliferation
6- Induce endothelial cell apoptosis

62
Q

What is one general limitation of targeted therapy?

A

They are specific only to one tumour cell phenotype and might not be suited for heterogenous tumours

63
Q

What are 4 targets of anti-angiogenesis therapy?

A

1- VEGF molecule
2- VEGF receptor
3- Signal transduction pathways induced by VEGF
4- VEGF protein translation

64
Q

What is the mechanism of anti-angiogenesis therapy that target the VEGF molecules?

A

Neutralizes VEGF protein and inhibits its biological action

Soluble VEGF receptors selectively bind to VEGF and prevent its binding to actual receptors

65
Q

What is the mechanism of anti-angiogenesis therapy that target VEGF receptor?

A

Acts as competitive inhibitors of the VEGF receptor

66
Q

What is the mechanism of anti-angiogenesis therapy that target the signal transduction pathways induced by VEGF?

A

Blocks the autophosphorylation (two subunits of VEGF receptor phosphorylate each other) of VEGF receptors

67
Q

What is the mechanism of anti-angiogenesis therapy that target VEGF protein translation?

A

These drugs have a nucleotide sequence that is antisense (ie complementary) to VEGF mRNA
They bind to VEGF mRNA and target degradation rather than translation

68
Q

In light of the evolutionary principles of cancer, what do you think is the major reason target therapy is rarely curative?

A

Most targeted therapies do not account for tumour heterogeneity. They typically eradicate the cells with the targeted phenotype quite well, but exert a strong selective pressure on the population of cells without that phenotype

69
Q

What are the 2 major cellular responses to therapy?

A

1- Induction of cell death

2- Evasion of therapeutic effect

70
Q

What are the 5 types of cell death?

A 
1- apoptosis
2- necrosis
3- senescence
4- mitotic catastrophe
5- autphagy
71
Q

What is the most common form of cell death?

A

apoptosis

72
Q

Describe apoptosis

A

regulated cell death induced either by the cell itself (intrinsic) or by external factors such as binding TNF-alpha to its receptor (extrinsic)
Both are mediated by caspase proteins

73
Q

Describe necrosis

A

unregulated, pathological cellular reaction to adverse cellular events, such as lack of cellular energy or overproduction of ROS
- Results in uncontrolled cell death and usually affects more cells than apoptosis-mediated cell death

74
Q

Describe senescence

A

Not technically cell death; cells that no longer have the ability to divide
Major cause if the shortening of telomeres signals to the cell to cease dividing

75
Q

Describe mitotic catastrophe

A

Cell death induced via aberrant mitosis

Improper segregation of chromosomes results in an irreversible trigger for cell death

76
Q

Describe autophagy

A

Process of cellular degradation in which a cell vacuole containing cellular components fuses with a lysosome

  • Not necessarily result in cell death; its occurs durong normal cell metabolism and can be used during starvation to recycle cellular contents
  • Can also occur as a result of cellular stress
77
Q

What are the 2 major categories of mechanisms by which cancer cells evade the effects of therapy?

A

1- host factors

2- cancer cell factors

78
Q

What are host factors and give 3 examples

A

Host factors often affect delivery of the drug to the tumour

  • rapid metabolism, absorption or excretion of a drug by the body
  • poor tolerance to the drug,s effect resulting in sub-optimal dosing
  • Inability to deliver drugs to the tumour due to size and/or blood perfusion
79
Q

What are cancer cell factors?

A

reduce the ability of drugs to affect cancer growth and are usually classed as drug resistance. They are natural cellular response to therapeutic pressure

80
Q

What are the 3 categories of drug resistance?

A

1- intrinsic
2- acquired
3- cross resistance

81
Q

Describe some features of drug resistance (3)

A

1- responsible for over 90% of treatment failure in patients with metastatic disease
2- can be triggered by the TME
3- has a multi-factorial origin

82
Q

What is intrinsic DR

A

Tumour does not respond to therapy following initial administration

83
Q

What is acquired DR?

A

Tumour becomes resistant after an initial successful response to therapy

84
Q

What is cross resistance DR

A

Resistance to first drug results in resistance to a second similar mechanism of action

85
Q

What are 6 cellular mechanisms of drug resistance?

A 
1- decreased drug uptake
2- increased drug efflux
3- metabolism: drug inactivation, decreased drug activation
4- alterations in drug target
5- DNA damage repair
6- Evasion of cell death
86
Q

Give an example of decreased drug uptake resistance

A

Decreased expression and/or mutations of the Reduced Folate Carrier 1 reduces the amount of methotrexate taken into the cell

87
Q

Give an example of increased drug efflux resistance

A

ATP-binding cassette (ABC) transmembrane proteins P-gp and MRP
transport drugs out of the cell, targeting naturally hydrophobic drugs like taxanes, anthracyclines, and vinca alkaloids and topoisomerase inhibitors

88
Q

Give an example of metabolism, drug inactivation, DR

A

5-FU is a chemotherapeutic agent that is normally broken down by dihydropyrimidine dehydrogenase (DPD) in the liver
- colorectal tumours resistant to 5-FU have been found to have increased levels of DPD
Platium drugs (cisplatin) can be inactivated by gluthatione (GSH) conjugation. GSH conjugate is a substrate of ABC pump
- high levels of GSH has been found in tumour cells resistant to platinum drugs

89
Q

Give an example of metabolism, decreased drug activation, DR

A

drug CPT-11 prevents cancer cell replication inhibiting the enzyme topoisomerase II
- It can be inactivated by cytochrome P450 enzymes, which are present in many cells to convert drugs to inactive forms

90
Q

Give 2 ways alterations in drug target can cause DR

A

1- decreased expression levels

2- Changes in microtubule dynamics and/or levels

91
Q

Give an example of decreased target expression resistance

A

5-FU targets thymidylate synthase (TS), and enzyme necessary for DNA replication

  • TS levels determine 5-FU sensitivity
  • Low tumour TS levels correlate with improved response in patients with colorectal and gastric cancer; high TS expression correlates with increased 5-FU resistances
92
Q

Give an example of changes in microtubule dynamics and/or levels resistance

A

Taxanes act on cells by inhibiting the microtbule movement required for division
- Taxane-resistant breast cancer cells have been shown to upregulate isoforms of microtubules not targeted by taxanes

93
Q

Give an example of DNA Damage repair resistance

A

Capacity to repair DNA determines resistance to DNA-damaging drugs
Ex: cancer cells can repair damaged DNA using the nucleotide excision repair (NER) pathway
- defects in this pathways result in hypersensitivity to cisplatin

94
Q

Give an example of evasion of cell death resistance

A

Mutations in p53 or cell cycle checkpoint proteins are common mechanisms of evading apoptosis inhibitors are in clinical trials

95
Q

Do individual cancer cells develop cellular mechanisms of DR in response to therapeutic pressure?

A

No. Cells that have acquired the mechanisms of DR via random mutations or inheritance have an increased survival advantage when therapeutic pressure is applied. Population of these cells are usually enriched after therapy because cells without these mechanisms are eliminated by the therapy
Individual cells cannot “develop” traits that it needs in response to selective pressure

96
Q

How does the TME affect cancer therapy response?

A

TME is a critical determinant in the selection of cells with malignant properties

  • Tumours have diverse TME incorporating many differente cell types
  • TME changes over time even within the same lesions and has been shown to change response to therapy
  • Dynamic interaction between tumour cells and their microenvironment; this interaction shapes the TME and, consequently, the selection of tumour cell variants
  • differences in selective pressure (hypoxia, acidity, and the presence of growth factors) exist within a tumour and actively shape its evolution
  • non-transformed cell types (pericytes or fibroblast) with TME adap to the phenotype of the tumour cells, so that both participated in process of tumourigenesis and malignant progression
  • all components in the TME can contribute to resistance to therapy
97
Q

What is one of the mechanisms of cancer-associated fibroblast (CAF)-mediated resistance, as identified in the article? (influence of tumour micro-environment heterogeneity on therapeutic response

A

CAF secretion of hepatocyte growth factor HGF has been shown to contribute to resistance of BRAF-inhibition in cells with the common V600E mutation

98
Q

What is on mechanism of endothelial-cell mediated resistance?

A

Endothelial cells have been shown to produce growth factor cytokines such as IL-6 in areas like the thymus in response to chemotherapy. This renders these areas vulnerable to tumour growth

99
Q

What TME factors contribute to drug resistance? (5)

A 
cell-cell contact
glucose concentration
pH
hormones
hypoxia
100
Q

What kind of selective pressure does oxygen-dependent chemotherapy put on cancer cells?

A

Cancer cells with the ability to survive without oxygen (survive in hypoxic conditions) will also be able to evade the therapeutic effects of chemotherapy. This selects for the survival of hypoxic cells and also make very hypoxic tumours difficult to treat with chemo

101
Q

What problem does cellular heterogeneity pose to cancer treatment?

A

Cancer treatment often targets specific cells, which does not address the diverse phenotypes present in heterogeneous tumours. This can lead to treatment-resistant cancer cells

102
Q

What are 4 ways to address the problem of tumour heterogeneity/not impose selective pressure that can result in aggressive clones?

A

1- targeting Cancer stem cells
2- Target tumour micro-environment
3- manage, not cure
4- focus on prevention

103
Q

How does targeting CSCs help address tumour heterogeneity?

A
  • can cut off the supply of new clones and avoid putting pressures on existing ones
  • CSC population may be re-established via dedifferentiation of progeny and they exhibit relative resistance to cytotoxic chemotherapy
  • chemotherapy and radiation therapy may stimulate tumour cell self-renewal through cytokine production and DNA repair mechanism
104
Q

How does targeting the TME help address tumour heterogeneity?

A
  • Alter TME to deprive all clones of valuable nutrients and oxygen could level the playing field for all clones
  • Does pose risk of selecting for clones that can live without said nutrients and oxygen such as selecting for hypoxia-resistanc cells
105
Q

How does focusing on managing and not curing address tumour heterogeneity?

A

by focusing on delaying cell division and maintaining tumour size, it could avoid placing selective pressure on cancer cells
mice with ovarian tumours can survive indefinitely if the tumours are treated to maintain size and not be eradicated

106
Q

How does focusing on prevention address tumour heterogeneity?

A

Tumour heterogeneity is not an issue because the cancer has not progressed to a high state of heterogeneity
eg: early detection

107
Q

Does combination chemotherapy wholly address tumour cell heterogeneity? why or why not?

A

Its imposing different selective pressure on a tumour cell population, which will decrease the chance of any sub-clone populations survivint. It is inevitable that there will be a resistant cell population in certain individuals, particularly in more advanced cancers with higher levels of heterogeneity
Also, any clones that do survive combination chemotherapy will be aggressively drug resistant. If these were to repopulate the tumour, the patient’s likelihood of cross resistance would be high

108
Q

Why is it important to determine the cellular origin of breast cancer?

A

This helps target effective treatment strategies and also aids in developing effective cancer prevention strategies

109
Q

What is the mechanism through which breast cancer stem cells (BCSCs) transition through the two states identified in the article? (Therapeutic implications of cellular heterogeneity and plasticity in breast cancer)

A

Epigenetic alterations regulated by the TME have been shown to mediate the transition between proliferative and quiescent BCSC states. These include cytokine and chemokine signalling as well as transcriptional regulation

110
Q

If dormant cells are not dividing or metastasizing, why is it important to target them at all?

A

All dormant cells have the potential to become active again, particularly those in angiogenic or immunologic dormancy. Consideration does not need to be given to the necessity of targeting cells in cellular dormancy. However, it may be that therapeutic intervention only occurs once cells have become active

111
Q

What are 2 approaches for directing therapy at dormant cells?

A

1- Manipulate transition

2- Targeting Dormant cells

112
Q

How does manipulating transition help treat dormant cells?

A

Therapeutics that can triger cells into of out of dormancy could be useful for targeting dormant cells and forcing aggressive cancer into a dormant state

  • provides a solution for treatment resistant dormant cells if therapy can promote re-entry into the cell cycle dormant cells can be targeted with conventional therapy
  • epigenetics have been shown to play a key role in dormant state switches histone-modifying drugs could be a promising target of dormant cells
113
Q

How does targeting dormant cells help treat cancer?

A

May be necessary to ensure dormant cells do not become active again
- however it is difficult without damaging quiescent normal cells like stem cellls. To do so, we’d need to identify molecular pathways that maintain dormancy
stress signalling pathways have been shown to be upregulated in dormant, but not quiescent, cell types and may represent a target

114
Q

Why is it that some cancers are cured in response to therapy and some are not? apply evolutionary principles of cancer to answer this question?

A

It boils down to tumour heterogeneity.
Compared with tumours with low heterogeneity, tumours with high heterogeneity have a higher likelihood of harbouring cell variants that are resistant to various therapies or of generating tumour cells capable of metastasizing prior or during therapy. Higher degree of evolutionary fitness

CANC380 (6 decks)

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