ANTINEOPLASTICS

Factors Affecting Penetrability

Modifier genes
Carcinogens

Estrogen

Hormonal/
reproductive
Repair enzyme factors

Response to
DNA damage
 Warning signs of Cancer

Change in bowel Sore that Unusual

movement and does not bleeding/discharge
bladder habits heal
 Warning signs of Cancer

Obvious change in wart or mole

Difficulty in swallowing

Nagging cough or hoarseness

 5 Types of Cancer

• Leukemia – ↑ WBC
• Sarcoma – connective tissue(bone)
• Melanoma – pigment producing cells(melanocytes)
• Carcinoma – epithelial cells(most common)
• Lymphoma – lymph nodes
 Tumor Markers
• PSA – Prostate Specific Antigen (Prostate Cancer)
• AFP – Alpha Feto Protein (Liver Cancer)
• CEA – Carcino Embryonic Antigen (Colon Cancer)

*Diagnosis: Imaging Studies, Biopsy

 Pathophysiology of cancer

There are three phases of development

involved in the formation of cancerous
growth.

1. Mutation
2. Promotion
3. Metastasis
 Normal Cell Growth: The Cell Cycle
2 homologous pairs are shown G1 (cell growth)

M (mitosis)
Oncogenes

Tumor
G2 suppressor
genes

DNA repair
genes

S (synthesis)
Don’t just read pls do understand….. :-D
• The cell cycle is a critical process that a cell undergoes in order to copy itself
exactly. Most cancers have mutations in the signals that regulate the cell’s cycle of
growth and division. Normal cell division is required for the generation of new cells
during development and for the replacement of old cells as they die.
• Most cells remain in interphase, the period between cell divisions, for at least 90
percent of the cell cycle. The first part of the interphase is called G1 (for first gap),
followed by the S phase (for DNA synthesis), then G2 (for second gap). During G1,
there is rapid growth and metabolic activity, including synthesis of RNA and
proteins. Cell growth continues during the S phase, and DNA is replicated. In G2,
the cell continues to grow and prepares for cell division. Cell division (mitosis) is
referred to as the M phase. Cells that do not divide for long periods do not
replicate their DNA and are considered to be in G0.
• In normal cells, tumor suppressor genes act as braking signals during G1 to stop or
slow the cell cycle before S phase. DNA repair genes are active throughout the cell
cycle, particularly during G2 after DNA replication and before the chromosomes
prepare for mitosis.
CANCER CHEMOTHERAPY

1.Alkylating Agents
2.Antibiotics
3.Antimetabolites
4.Plant alkaloids
5.Hormones
6.Enzymes
 ALKYLATING AGENTS

ALKATING AGENTS

Nitrogen mustards Ethylenimenes/ Platinum Coordination

Alkylsulfonates Nitrosoureas Triazines Substituted urea Others
Methylmelamines Complex

Mechlorethamine

Thiotepa Busulfan Carmustine Dacarbazine Cisplatin Hydroxyurea Procarbazine

Chlorambucil

Ifosfamide Altretamine Lomustine Carboplatin Temosolamide

melphalan
SAR ALKYLATING AGENTS

MECHLORETHAMINE

CIS POSITION!

CISPLATIN
 Alkylating Agents
• Cisplatin & Carboplatin
– Treatment of ovarian cancer

• Chlorambucil
– DOC of Chronic Lymphocytic Leukemia (CLL) & non-
Hodgkin’s Lymphoma (NHL)

• Cyclophosphamide & Ifosfamide

– Converted to acrolein (causes hemorrhagic cyctisis)
• prevented by MESNA (Na-2-mercaptoethane sulfonate)
 ANTITUMOR ANTIBIOTICS
MoA: Intercalation

Anthracyclines Anthracenendiones
Other agents

Bleomycin
Daunorubicin
(daunomycin) Methoxanthrones

Dactinomycin
Doxorubicin (Adriamycin, (Actinomycin D)
hydroxydaunorubicin)

Plicamycin
Idarubicin (Mithramycin)
 Other anthracyclines are quite similar
DNA intercalating chromophore with changes only in the methyl radical
(pale yellow) of the inversion of
hydroxyl and hydrogen.

Minor groove
binding moieties
Enzyme interacting
domains

Topoisomerase II poisoning
 Antitumor Antibiotics
• Daunorubicin/Daunomycin
CARDIOTOXIC
• Doxorubicin
– Dexraxozane(cardiac protectant)
• Bleomycin & Busulfan
– Pulmunary toxicity (Pulmunary fibrosis)
 ANTIMETABOLITES
MoA: inhibit DNA synthesis

Adenosine Folic acid Purine analogs/purine Pyrimidine analogs/

analogs analogs antagonist pyrimidine antagonist

Cladribine Methotrexate Mercaptopurine Capecitabine

Fludarabine Thioguanine Cytarabine

Fluorouracil

Gemcitabine
METHOTREXATE
METHOTREXATE
6-MERCAPTOPURINE Substitution of:
alkyl, halogen, cyano, and
carboxy
= inactive / ↓activity

Substitution = inactivate
 Antimetabolites
• Purine Antagonist
– Mercaptopurine
– 6-Thioguanine
• Pyrimidine Antagonist
– Cytarabine
– Fluorouracil
• Folic Acid Analog
– Methotrexate: inh DHFR → inh DNA Synthesis → Folic Acid
deficiency (Leucovorin/ Folinic Acid)
• Cancer
• DMARD
• Ectopic Pregnancy
 PLANT ALKALOIDS

Vinca Camptothecins Podophylo- Taxanes

Alkaloids MoA: prevent
Toxins
MoA: prevent MoA: inhibit microtuble
formation of topoisomerase I MoA: inhibit assembly and
mitotic spindle topoisomerae II stabilization

Docetaxel
Vincristine Irinotecan Etoposide
(Taxotere)

Paclitaxel
Vinblastine Topotecan Teniposides
(taxol)
VINBLASTINE
 Plant Contituents
• Vinca Alkaloids
– Catharanthus roseus
• Podophyllotoxins
– Mandrake/Mayapple (Podophyllum peltatum)
• Taxanes
– Taxol (tx of ovarian, breast & lung cancer)
• Camptothecins
– From the bark & stem of Happy Tree
(Camptotheca acuminata)
Hormones
TAMOXIFEN

Essential for activity

 Hormones
• Anti-androgen (Flutamide)
– Normal PSA, enlargement: Benign Prostatic
Hyperplasia
– Diagnosis: DRE (Digital rectal exam)
• Anti-estrogen (Tamoxifen)
– Estrogen-dependent breast cancer
– Diagnosis: Mammography (breast cancer);
Papsmear (Cervical Cancer)
– A/E: Endometriosis