Antineoplastic Drugs I

Surgery, Radiation therapy, Chemotherapy

Immunotherapy, Targeted therapy, Photodynamic therapy, Gene therapy

• grow slowly
• well defined capsule
• non-invasive
• well differentiated (how well cancer cells resemble regular cells)
• low mitotic index
• non metastasizing

• grow rapidly
• not encapsulated
• invasive
• poorly differentiated
• high mitotic index
• metastasizing

Normally a growth factor would bind to a receptor and result in cell replication. In a cancer cell there is a mutation where this is signaling of a cell replication without the ligand.

Oncogenes - "good guy turned bad"

• Encodes proteins that in their normal state negatively regulate proliferation.
• Also called anti-oncogenes

Proto-oncogene

True.

1) TP53 - receives inputs from stress and abnormality sensors from within the cell's intracellular operating systems and leads to apoptosis.

2) RB (retinoblastoma-associated protein) transduces growth inhibitory signals that originate largely outside of the cell. Stops cell from going to S phase.

P53. activated in a number of ways including chemotherapy and radiotherapy which cause DNA damage.

• By activating telomerase.
• Telomeres are protective caps on each chromosome and usually become smaller and smaller with each cell divison. In cancer they somehow activate telomerase and limitations of mitosis are not a problem anymore.

• True.
• Examples of activators include: VEGF-A, B, C, FGF1, FGF2
• Examples of inhibitors: thrombospondin 1,2, interferon alpha and beta, angiostatin, endostatin, collage IV fragments

• 1) Localized invasion - the tumor is formed and grows slowly toward capillary
• 2) Intravasation - cancer cells fit through the endothelial lining of blood vessels and circulate throughout body
• 3) Extravasation - while circulating it fits through the endothelial lining of blood vessels into sometype of organ/tissue
• 4) Formation of micrometastasis
• 5) Colonization - formation of macrometastasis

False. Only some cancers are inheritable.

• Point mutations
• chromosome translocations
• gene amplification
• mutation of tumor-suppressor genes
• loss of herozygosity
• gene silencing
• chromosome instability
• Epigenetic changes - DNA regulation change, NOT sequence change. ex: histone defect

• 1) Inflammation
• -Cytokine release from inflammatory cells.
• -Free radicals
• -Promotion of mutations
• -Decreased response to DNA damage

• 1) Chemicals : carcinogen
• 2) Viruses: Hep. B & C, Epstein-Barr virus, Kaposi sarcoma herpesvirus, HPV, Human T-cell leukemia-lymphoma virus
• 3) Bacteria: Helicobacter pylori
• 4) Ionizing radiation, UV radiation, Electromagnetic fields, Cancer treatment

• M phase is mitosis which includes the prophase, metaphase, anaphase and telophase.
• G0 phase is the resting phase in terms of cell growth.
• G1, S and G2 phase is collectively known as Interphase
• G1 phase is a period where cells are responsive to mitogenic GF's and TGF-beta. Entrance into S phase is blocked if there is any DNA damage
• S phase is a period where DNA synthesis occurs. DNA replication is halted if the genome is damaged
• G2 phase period where microtubules are formed before the M phase. Entrance into M phase blocked if DNA replication is incomplete.

The suggestion that a fraction of cancer cells always rest in G0 phase and therefore are NOT sensitive to chemotherapy.

False. Refer to log-kill hypothesis. It takes many cycles to kill all the tumor cells. May take many years.

True

Bone marrow, GI, and hair follicle cells

• Nausea/Vomiting
• Diarrhea
• Hair loss

True

• It decreases chance of resistance to chemo drugs.
• Aim for maximal cytotoxicity with tolerated host toxicity

• 1.Reduced drug uptake
• 2. Enhanced EGFR/MAPK/ERK signaling --> enhances proliferation
• 3. Inhibition of apoptosis
• 4. Changes in drug-target interaction
• 5. Enhanced drug inactivation
• 6. Reduced drug activation
• 7. Enhanced drug export

• -Efficacy: only drugs known to be somewhat effective against same tumor when used alone
• -Toxicity: Drugs with little overlapping toxicity. Broadens ADRs but improves tolerance of single organ/system
• -Optimum scheduling: drug combos should be given at consistent intervals for recovery
• -Mechanism: synergistic effect whenever possible. different MOA
• -Avoid arbitrary dose changes

True