Unit 09 Cancer background

Question 1

What are the classes of anticancer drugs

Answer 1

• Acts on DNA
  
  • Damanges DNA
    
    • Alkylating agents
    • free radicals/intercalating agents
  • Inhibit synthesis
    
    • Antimetabolites
• Inhibits chromatin function
  
  • Topoisomerase inhibitors
  • microtubule inhibitors
• Acts on hormone.steroid receptors
  
  • Agonist
  • antagonist

Question 2

what is malignant neoplasm

Answer 2

name for cancer

• cells grow uncontrollably, invade surrounding tissue and sometimes colonize other locations in the body (metastasis)

Question 3

what is angiogenesis

Answer 3

growth of new blood vessels from existing vasculature

-critical part of tumor growth bc allows new abnormal cells to cont to grow by providing oxygen and nutrients

Question 4

how to tumors induce blood vessel growth

Answer 4

secret growth factors

• blood vessel growth also related to metastasis (colonization of other locations in body) - cells move away from primary tumor and invade other parts of body through blood or lymph

Question 5

what is the most feared and least understood aspect of cancer?

Answer 5

Metastasis

• patients suffering from cancer will die from secondary disease, not the original tumor
• occurs when cells detach from parent tumor and enter blood or lymph vessel, exit from ciruclation and proliferation in the new environment

Question 6

What is a carcinoma?

Answer 6

• cancers of epithelial cells lining surface of organs

Question 7

what are sarcomas

Answer 7

cancers of muscle, bone, cartilage, fat or connective tissue

Question 8

what is leukemia?

Answer 8

cancer of white blood cell or blood precuror cells

Question 9

what is lymphoma

Answer 9

cancer of bone marrow derived cells that affectt he lymphatic system

Question 10

what are blastomas

Answer 10

cancers throught to arise from immature or embryonic tissue

Question 11

80-90% of acll cancers are _____

Answer 11

carcinomas

means that cell proliferation and frequent exposure to chemical and or physical change

Question 12

how do most cancer cells originate?

Answer 12

• originate from a single aberrant (abnormal) cell
• abnormal cell might have been result of genetic mutation (change in cell DNA) or epigenetic mutation change in gene expression without change in DNA

*cells have normal mutation, single mutation not enought ot cause cancer its several independnt changes in cell lineage

Question 13

main factors influencing tumour progression

Answer 13

mutation rate, number of cells in population, rate of cell division and selective advantage

Question 14

what genes play a critical role in cancer developmen and progession?

Answer 14

• DNA proofreading and reapid genes, genes that maintain chromosomal integrity, oncogenes, tumour suppressor genes

Question 15

effects of mutations in genes that regulate DNA repair

Answer 15

• cells susceptible to endogenous and exogenous damage throughout life cycle
• in healthy cell, damage to nuclear or mitochondrial DNA will be fixed bc rate of damage = to rate of repair
• in pathological situations rate of damage > rate of repaire
• mutations can be inherited, unstable cells are less fit and tend to aquire additional mutations in cell death, differentiation or division more frequently than normal cells

Question 16

what are oncogenes

Answer 16

oncogenes aquire “gain of function” mutation vs tumour suppressor genes acquire “loss of function”

oncogene ex: hormones or growth factors, receptors, cell signaling molecules and transcription factors

Gain of function: mutated oncogenes are expressed at high levels resulting in cell growth and an inc in mitosis (cancer)

Question 17

what are tumour suppresor genes

Answer 17

• kind fo like anti-oncogenes - protect cells from cancer pathology
• mutations to these genes are loss of function mutations : mutated oncogenes are expressed at high levels resulting in cell growth and an inc in mitosis

mutation in genes that normally suppress mitosis and cell growth or induce apoptosis leads to loss of function

Question 18

what is the goal of cancer therapy and principles

Answer 18

• prevent, cure or control the disease
• for some terminal patients in palliative care it focuses on relieving and prevening suffering

Principles:

1. cure requires death of ALL tumour cells
2. Drugs kill a constant proportion of tumour cells
3. Tumours detected later require prolonged treatment
4. Drugs have narroe therapeutic index
5. Drug combinations can increase effectiveness and decrease adverse effects
6. Intermittent high dose therapy is more effective
7. Adjuvant therapy may decrease metastases

Question 19

localized vs systemic cancer treatment

Answer 19

• surgery and radiation = localized treatment bc its to a specific region(s) of body
• chemo and hormone therapy = systemic treatment bc they afffect all regions

*chemo can be used alone or in addition to radiation or surgery, if applied before the goal is to shrink the tumor before removing it, if applied after goal is to kill remaining cancer cells

Question 21

what types of factors influencer cancer patient survival

Answer 21

• nature of cencer itself: typce, stage, time of diagnosis, growth rate, heterogeneity of cells within tumour and cell-cycle phase
• general health, tumour blood supply and immune status also play important roles

Question 22

phases of cell division and in what phase are drugs usually most toxic?

Answer 22

• G0, G1, S, G2 and M phases
• many drugs are most toxic during S-phase, somewhat effective during M phase and most are ineffective during G0 phase

Question 23

how does growth rate affect chemotherapy treatment?

Answer 23

• growth fraction refers to percent of dividing cells that ae sensitive to chemo
• addition of therapeutics during proliferative phase would allow slow growing tumours to be treated early
• early metastatic lesions have been shown to ahve a high growth fraction and fast growing cancers are more responsive to treatment

Question 24

kinetics of chemotherapy

Answer 24

• Chemotherapy kills cancer cells via first order kinetics- eliminaition of drug is proportional to plasma conc of same drug

Question 25

why do anticancer drugs fail?

Answer 25

due to lack of specificity (side effects and dosage limitations) or fact that cancer is resistant to treatment

• some neoplastic cells are inherently resistant others develop mutations throughout growth leading them to develop or acquire resistance
• multidrug resistance may also ocur, involved a selection of cells expressing amplified p-glycoprotein that pumps drugs out of cell

Question 26

what are some of the side effects of chemotherapy?

Answer 26

major sites of toxicity are bone marrow (myelosuppression), Gastrointestinal tract (vomiting, nausea and diarrhea), hair follicles (alopecia), reproductive tract (dec sperm count, menopause and teratogenicity) and secondary carcinogenicity

Question 27

what is most effective way of administering chemotherapy

Answer 27

• using in combination
• use drugs that offer synergistic action and have diff MOA and resistance pathways (no overlap in toxicities) are ideal
• want to give as close to maximal effective dose and give frequently to discourage cancer growth

Question 28

what are the main factors influencing dosage of chemotherapy?

Answer 28

dosage is primarily based on body surface area but pharmacokinetics like hepatic and renal function also considered

• type of cancer, patient health, desire to undergo difficult/dangerous treatment and ability to cope with side effects are also important