Anti-Cancer Drugs

cancer

condition where abnormal cells persistently divide and grow without control

tumor

an abnormal tissue growth that forms a mass

benign

a tumor that does not invade nearby tissue and does not spread to other parts of the body

malignant

a tumor that invades nearby tissue or spreads throughout the body

metastases

secondary tumors at sites distant from the original tumor

tumor cell process

1. normal cells →

2. abnormal cells →

3. abnormal cells multiply →

4. malignant cancer

angiogenesis

cancer grows its own blood vessels from existing blood vessels; invades surrounding tissue

ideal cancer drug

effectively kills specific tumor cells; selectively kills tumor cells, but does not cause harm to normal cells in the body; does not have side effects; given only a few times intermittently (not continuously); tumor cells do not develop resistance to the drug

anticancer drug classes

1. cytotoxic drugs - broad spectrum

2. hormonal drugs - breast / prostate cancer

3. biologic response modifiers - boost immune system to fight cancer cells

4. targeted drugs - specific cellular target

cytotoxic drugs

largest class of anticancer drugs; 7 major groups; act directly on cells to cause cell death; “hitting a nail with a sledgehammer”

growth fraction

the ratio of proliferating cells to resting cells

cell cycle

1. growth fraction

2. G1 - preparation for DNA replication (cell proliferation)

3. S - DNA replication (cell proliferation)

4. G2 - preparation for cell division

5. M - cell division (mitosis)

6. G0 - quiescence (resting)

cytotoxic drug classes

1. antimetabolites

2. antitumor antibiotics

3. mitotic inhibitors - vinca alkaloids / taxanes

4. alkylating agents - nitrogen mustards / nitrosoureas

5. platinum compounds - alkylating “like”

6. topoisomerase inhibitors

7. misc.

antimetabolite drug groups

1. folate analogs - folic acid required for the synthesis of purines / pyrimidines

2. purine analogs (adenine [A], guanine [G]) → Pure as gold (AG)

   -6-mercaptopurine

3. pyrimidine analogs (thymine [T], cytosine [C]) → CUT the Py

   -5-fluorouracil

alkylating / “like” drugs - DNA attacks

1. bifunctional alkylation

2. mono-functional alkylation

bifunctional alkylation

some drugs become inserted between 2 base pairs in the DNA chain, forming an irreversible bone between them; causes cytotoxic effects capable of destroying or poisoning cells

monofunctional alkylation

other drugs react with just one part of a pair, separating it from its partner and eventually causing it and its attached sugar to break away from DNA molecule; eventually may cause permanent cell damage

cytotoxic drug therapy

combination drug therapy is most effective due to less drug resistance, increased effectiveness when drugs with different mechanisms can be combined, and being less toxic to normal cells because drugs with non-overlapping toxicities are used; intermittent dosing allows normal cells to repopulate between drug treatments → less normal cell toxicity

Hodgkin’s cancer

type of cancer that affects the lymphatic system, which is part of the immune system; drugs = adriamycin, bleomycin, vinblastine, dacarbazine (ABVD)

breast cancer

disease that occurs when breast cells grow out of control and form tumors; drugs = cyclophosphamide, methotrexate, 5-fluorouracil (CMF)

anticancer drug handling

drugs can be carcinogenic, teratogenic, and/or caustic; direct contact can cause local injury and cancer risk; handle with care; extravasation of caustic drugs (vesicants - doxorubicin, vincristine, dactinomycin, etc.) can cause severe local injury

guiding principles for targeted drugs

1. ER - estrogen

2. PR - progesterone

3. HER2 - Human Epidermal growth factor Receptor 2

when expressed, these receptors can be specific targets to kill the cancer

hormonal drugs for prostate cancer

prostate gland tumors require androgen for tumor growth; treatment = surgery, radiation, and antiandrogen therapy (androgen deprivation therapy); drugs = GnRH antagonists and androgen receptor blockers

targeted drug classes

1. antibody drugs - “biologics”

2. synthetic drugs

3. angiogenesis inhibitors - bevacizumab

4. CAR T-cell therapy

imatinib

targeted drug; translocation (break / exchange between chromosomes 9 and 22) brings together ABL (Philadelphia chromosome); >95% of chronic myeloid leukemias have this genetic marker (Ph + CML); BCR-ABL encodes a novel cytoplasm-targeted tyrosine kinase that allows cells to proliferate without endogenous regulation

other drugs / purposes

1. EGFR inhibitors - sustaining proliferative signaling

2. cyclin-dependent kinase inhibitors - evading growth suppressors

3. immune activating anti-CTLA4 mAb - avoiding immune destruction

4. telomerase inhibitors - enabling replicative immortality

5. selective anti-inflammatory drugs - tumor-protecting inflammation

6. inhibitors of HGF/c-Met - activating invasion / metastasis

7. inhibitors of VEGF signaling - inducing angiogenesis

8. PARP inhibitors - genome instability / mutation

9. pro-apoptotic BH3 mimetics - resisting cell death

10. aerobic glycolysis inhibitors - deregulating cellular energetics