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Chemotherapy: Cancer Flashcards

1
Q

Chemotherapy generally a second choice in

A

cancer

(commonly as adjuvant, neoadjuvant)

more responsive to lymphomas, leukaemia, testicular

in general - cancer in old age
leukaemia - children

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2
Q

1st choice for solid tumour

A

Surgery

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3
Q

IV or oral ie. systemic delivery/absorption
‘Finds’ the cancer cells wherever they are
better in non-solid tumours
but normal cells also affected

A

Chemotherapy

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4
Q

more selective/target therapy towards tumour

A

Immuno therapy

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5
Q

Characteristics of cancer cell

A 
1. Uncontrolled proliferation 
Cancer grows more and more!!!! Number increased!!! lose control signals
2. loss of function/differentiation
3. invasiveness
4. metastases
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6
Q

Molecular basis of chemotherapy: aim

A

to kills as many tumour cells as possible with each treatment
not to harm normal

Selective toxicity

Exploit differences between normal cells and cancer cells

But cancel cells are our own cells that are out of control

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7
Q

covalently bind to DNA and prevent replication

A

Alkylating agents

AFFECT THE DNA

modify DNA structure

covalent bonds, DNA helix X links intra- and inter strand, attach to free guanines at N6 on separated DNA strands, cannot act as template for new DN formation

Bifunctional - can crosslink - intra (strand cannot get out of alpha helical conformation-wont replicate) and inter-strand cross linking (two strand wont separate which they need for replication)

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8
Q

prevent the syn of DNA precursors

A

antimetabolites

AFFECT the DNA PRECURSOR

immune suppression, anti-cancer, psoriasis - methotrexate (folate antagonists)
pyrimidine and purine analogues

rem as: metabolite =precursor

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9
Q

prevent cell division

A

cytotoxic antibiotics

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10
Q

major classes of cytotoxic drugs

A
  1. Alkylating agents - cisplatin
  2. Antimetabolites - Fluorouracil (FU)
  3. Mitotic inhibitors - etoposide, taxoid, Vinca alkyloids
  4. antibiotics - mitomycin
  5. others - hydroxyurea

Most target DNA

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11
Q

mitotic spindle poisons
Inhibit MITOSIS
relative non-toxic cancer drug

A

Vinca alkyloids and related compounds

vin.. groups
bind to tubulin
arrest at metaphase

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12
Q

steroid

A

Hormones

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13
Q

GFs, oncogenes, cyclins and CDKs

A

promote cell cycle

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14
Q

TSG, CDK inhibitors

A

inhibit cell cycle

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15
Q

… are the guardians to check if cell damaged/needs repairing?

A

Restriction points

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16
Q

How do you deliver chemotherapy?

A

IV or oral

regular cycle - watch on pharmacokinetics
may be need for delay to allow normal cells to recover (but also a problem as tumours can also recover) - we do go down with cells we have got after each drug admin- may have residual leftover cancer cells
but later, patient cannot take any more chemotherapy - endpoint for their treatment intensify the drugs

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17
Q

Methods for assessing drug activity

A
  1. objective response in adv disease : CT scan, PET scan, smaller masses clinically
  2. improved - survival, progression free survival, QoL
  3. Adjuvant treatment
  4. Neoadjuvant
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18
Q

Add the chemotherapy after the surgery
(Chemotherapy mops up residual tumour cells)
improves survival (usually)

A

Adjuvant chemotherapy

highly targeted to the type of cancer - multiple drugs - used to prevent drug resistance

19
Q

Give the patient chemotherapy before the surgery

if big tumour, shrink more, better chance of success in removing the whole mass in the surgery

A

Neoadjuvant

20
Q

Toxic drugs that are anti-proliferative (stops cells growing both normal and cancerous), but doesn’t affect invasion nor metastasis

A

Cytotoxic agents

we have drugs that kills cells but do not have one for metastases or invasiveness

21
Q

Cisplatin (nephrotoxic) used for testicular cancer in young men - not an alkylating agent - but acts like one - adds platinum rather than alkyl group to crosslink the DNA strands

A

platinum (pos) bind with Neg DNA

22
Q

DNA are …. charged

A

neg

23
Q

drug commonly used in CRC (pyrimidine analogues)

A

5-FU (Fluorouracil)

analogue of uridine(forms a RNA base)

inhibits DNA & RNA syn by getting metabolised itself

5-FU > FUMP (blocks RNA) +FdUMP (blocks DNA)
lethal synthesis - cannot base pair - single stranded - susceptible to attack/dies

24
Q

intercalate and inhibit DNA/RNA syn

free radicals formation

A

antimitotic antibiotics

anthracyclines and non-anthracyclines

25
Q

inhibits topoisomerase ii (unwind DNA)
inhibit mitochondria function
nausea, vomiting, myelosuppression and alopecia

A

etoposide

26
Q

freeze microtubules
attack mitosis
effect In ovarian and drug resistant breast cancer

A

taxol

27
Q

….. Metastases common

A

Liver

28
Q

Chemotherapy

A

Systemic therapy

Chemotherapy won’t work at G0 phase
Work for S, M phase

29
Q

Breast and bowel

A

routine neoadjuvant

For lung - not used routinely

30
Q

alkylating agents

A

cisplatin

31
Q

replication fork arrest and irreversible DNA breakage
cell cycle interruption
cell death

A

CPT 11 Irinotecan ‘plant alkaloid’

32
Q

prevent lymphocyte proliferation

side-effects with long-term treatment

A

Glucocorticoids hormones

immunosuppressive

33
Q

acute lymphoblastic leukaemia; lymphomas (Hodgkin’s and non-Hodgkin’s)
combination therapy

A

Glucocorticoids hormones(prednisolone)

34
Q

Sex hormones and antagonists

A

Response of tumour to sex hormones

dependent on receptor expression

35
Q

ER+ - growth dependent on oestrogen

block effect of oestrogen on tumour cells

A

Oestrogen

breast cancer

36
Q

binds to ER
no gene transcription
side-effects (blood clots, endometrial changes)

A

Tamoxifen (anti-oestrogen)

37
Q

Combine

Different mechanism of action

Dissimilar toxicity profile

A

Combination chemotherapy

Combine those with
Different mechanism of action
Synergistic or at least additive
Reduce risk of developing resistance

Dissimilar toxicity profile eg not both with neurotoxicity (cisplatin and taxane)
Give each to maximum tolerated dose

38
Q

Hormonal drugs
Anti-oestrogen Tamoxifen, aromatase inhibitors for breast cancer
Gonadorelin analogue eg Goseralin (Zoladex)
Anti-androgen (CPA, flutamide) for prostate cancer

A

Systemic Therapy

39
Q

Targeted drugs against
Epidermal growth factor receptor (EGFR) Gefitinib/Erlotinib
Vascular endothelial receptor (VEGF) Bevacizumab (Avastin)
Multiple targets sorafenib, sunitinib, etc

A

Systemic Therapy

40
Q

CINV

A

Chemotherapy induced nausea and vomiting

Acute response: Peripheral
Enterochromaffin cell
Serotonin release
Vagal afferent
5-HT3 receptors

Central
Brainstem
NK1 receptors
Substance P

Dorsal vagal complex
Area postrema

41
Q

Systemic therapy invoves: chemotherapy, and … drugs

A

Hormonal

Anti-oestrogen Tamoxifen, aromatase inhibitors for breast cancer
Gonadorelin analogue eg Goseralin (Zoladex)
Anti-androgen (CPA, flutamide) for prostate cancer

Targeted drugs against
Epidermal growth factor receptor (EGFR) Gefitinib - better
Vascular endothelial receptor (VEGF) Bevacizumab (Avastin)
Multiple targets sorafenib, sunitinib, etc

42
Q

The First PD-1 Inhibitor Proven to Significantly Improve Overall Survival vs. Docetaxel1

A

Nivolumab

43
Q

Chemotherapy side-effects

MAIN

A
  • Myelosuppression (bone marrow suppression)
  • Alopecia (hair loss)
  • Infection risk increased
  • Nausea

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