Anticancer Drugs 2 Novel anticancer agents

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Monoclonal antibodies
1) Immunize mouse to obtain
antibodies
2) Isolate antibody-forming
cells from spleen
3) Fuse these cells with
tumour cells to form
hybridomas
4) Hybridomas screening for
antibody production
5) Antibody-producing
hybridomas cloned
6) Antibiodies isolated for
cultivation
Optional: Attach cytotoxic
agent to cloned antibody
Rutiximab
Directed towards CD20
surface antigen overexpressed
on B cells in non-Hodgkins
lymphoma, triggering B-cell
lysis

Trastuzumab (Herceptin)
Binds to human epidermal
growth factor 2 (HER2) which
is overexpressed in some
breast cancer forms.
Treatment Complications
Drug resistance
Complication Spontaneous rapid
mutations allow cancer cell
to acquire adaptations that
protects it
Strategies

1) Multiple cytotoxic drug

therapy Multiple drugs
with differing actions
2) Drug holiday: Attack at
different times when
different cells are at cell

Biological response modifiers

Immune system cannot (by
itself) detect and remove cancer
cells.
Desired action is to remove
immune cells and modify them
to detect cancer.
Limitation: Limited cancers

Interferons
- Augments the cytotoxicity of
immune cells
- High doses inhibit cell
proliferation, facilitate
cytotoxicity
- Alter antigen expression on
tumour cells and immune cells

Tumour cell sanctuaries

Tumour cells grow in

compartments that are
inaccessible to drugs,
creating sites of relapse
Radiotherapy and
surgery on top of drugs
E.g. brain, due to
blood-brain barrier

Cytokine treatment
Process (interleukin-2)
1) Remove patients
lymphocytes and grow
in culture
2) Sensitise them
against tumour cell
antigens
(culture+antigen+IL2)
3) Reinject these cells
that are more
aggressive against
tumour

Interleukin-2 (IL2)
Stimulates lymphocyte
proliferation and
cellular immunity
Works on various cells
NK, T/B

Dose exhaustion
Maximum therapeutic
dose and immune
response of patient
not enough to attack
remaining cells; any
increase is toxic
Multiple drug therapy,
radiotherapy, surgery
and chemotherapy
combinations

Protein-kinase inhibitors
1) small molecule drugs bind
to enzymes ATP binding site
2) Inactivate the enzyme
3) Some may work to inhibit
angiogenesis as well.
Result Disrupt signalling
process, halts cell division
and proliferation
Limitation: Limited cancers
(leukaemia, GI tumours) &
cell may proliferate via other
signalling molecules
(Ras protein, cdks)

Sensitising agent
Urinary bladder tumour
- BCG used to immunise
against TB, but BCG can
also be used to make cells
more immunoreactive.
- Induces inflammatory
action, increases
likelihood cancer cells are
attacked by immune cells
(Cancer cells take up
BCG, immune system can
identify cancer cells)

Tyrosine Kinase:
Dasatinib, lapatinib etc.
Serine-threonine kinase
inhibitor:
B-raf proto-oncogene
sereine/threonine protein
kinase (BRAF)

Managing Adverse Drug Reactions

Antiemetic drugs (Prevent nausea/vomiting)
Dopamine, serotonin (via GIT), neurokinin receptor antagonists
(Prevent triggering of vomiting sensation in medulla of brain)
Maxalon (cheaper, first option), Ondensetron (expensive)..
Dexamethasone A glucocorticoid longer acting than
prednisolone that has antiinflammatory effects in GIT, decreasing
emetic stimuli to brain
Colony Stimulating Factors (CSFs)
Filigrastim (Increase WBC)
Erythropoietin (Increase RBC)
Organ toxicity
Mesna: Used in conjuction with cyclophosphamide and ifosfamide

Anticancer Drugs 2 Novel anticancer agents

cycle desired

to prevent bleeding in urinary bladder