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Drugs Used in the treatment of Cancer. Pharmacology 49.222 Bill Diehl-Jones RN, PhD Faculty of Nursing and Department of Zoology. Agenda. Zen Review What is cancer General goals in cancer treatment Targets of chemotherapy Targets of radiotherapy Breast cancer therapies

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Drugs Used in the treatment of Cancer

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drugs used in the treatment of cancer

Drugs Used in the treatment of Cancer

Pharmacology 49.222

Bill Diehl-Jones RN, PhD

Faculty of Nursing and Department of Zoology

  • Zen Review
    • What is cancer
  • General goals in cancer treatment
  • Targets of chemotherapy
  • Targets of radiotherapy
  • Breast cancer therapies
  • Prostate cancer therapies
characteristics of cancer cells
Characteristics of Cancer Cells
  • The problem:
    • Cancer cells divide rapidly (cell cycle is accelerated)
    • They are “immortal”
    • Cell-cell communication is altered
    • They can disrupt normal, healthy tissues
anticancer drugs
Anticancer Drugs
  • Some Solutions
    • Most cancer chemotherapies are designed to “hit” cell replication
  • A problem:
    • This approach is non-specific
    • Most cancer chemotherapies kill cancer cells only slightly faster than normal cells
targets of anticancer drugs
Targets of Anticancer Drugs:

Inhibitors of

DNA Synthesis

(Mercaptopurine, Methotrexate)


Inhibitors of

DNA Function

(Doxorubicin, Cisplatin)



Inhibitors of

DNA Replication

(Cytochalasin, Vincristine)


the goal of cancer treatments
The Goal of Cancer Treatments
  • Curative
    • Total irradication of cancer cells possible?
    • The concept of “log kill”
      • If 109 cells present, and tmt kills 99.999%, then 0.001% left
      • This is a 5-log kill
  • Palliative
    • Alleviation of symptoms
    • Avoidance of life-threatening toxicity
cell cycle dependant vs cell cycle independent drugs
Cell Cycle-Dependant vs. Cell-Cycle Independent Drugs
  • Some drugs kill cancer cells only at certain phases of the cell cycle:
    • Eg: Cytochalsin
    • Works only when a high ppn of cells are dividing
  • Some drugs work throughout cell cycle:
    • Eg: Cisplatin
some general chemotherapy concepts
Some General Chemotherapy Concepts
  • Most drug therapies are combination
    • Eg: for ALL
      • “POMP”: Prednisone, Oncovin, Methotrexate, Purethinol
  • Most chemotherapeutics have very low Therapeutic Indices
  • Some treatments themselves may induce tumors
hormonal theory of breast cancer
Hormonal Theory of Breast Cancer
  • Reproductive risk factors include:
      • Early puberty, late menarche, short duration of breast feeding, nulliparity, delayed child birth
  • Theory:
      • prolonged exposure to estrogen may initiate breast cancer
exposure to estrogen like compounds confers risk of breast cancer

Exposure to Estrogen-like Compounds Confers Risk of Breast Cancer

They may bind to same receptors, yield similar metabolites



Free Radicals


Estrogen/Estrogen-like Molecules

Induce Cell-Proliferation Genes

Estrogen/Estrogen-Like Metabolites

Form DNA Mutations

OH•, O•

dna adducts why are they problematic


















DNA AdductsWhy are they problematic?
  • Adducts may disrupt key regulatory pathways in ductal cells
      • Eg: p53, ras
  • Adducts can cause gene mutations:
blocking estrogen receptors
Blocking Estrogen Receptors
  • Principle drug is TAMOXIFEN
    • Competes with estradiol for binding sites
    • Works in ER+ cancers
    • Often used in breast cancers which have metastasized to bone
      • May cause pain in affected site: a GOOD sign!
    • May cause eye damage
aromatase inhibitors

Aromatase Inhibitors

A New Class of Breast Cancer Drugs

NOT ER+ Dependant

estrogen from two sources may initiate breast cancer
Estrogen from Two Sources May Initiate Breast Cancer:









Endogenous Estrogen

Due to aromatase overexpression

aromatase inhibitors20
Aromatase Inhibitors
  • While Tamoxifen blocks a tumor’s abitlity to use estrogen, AI’s reduce the amount of estrogen in the body
  • Three AI’s currently approved:
    • Anastrazole (Arimidex®)
    • Exestane (Aromasin®)
    • Letrozole (Femara®)
the bottom line
The Bottom Line
  • A major study of AI’s:
    • Breast cancer survivors taking letrozole after completing 5 years tamoxifen theraoy had significantly lower recurrence of breast cancers than women NOT on letrozole
prostate cancer
Prostate Cancer
  • “It doesn’t matter who you are … if you are male and live long enough, you WILL get prostate cancer”
    • Bill Jones Sr.
how is prostate cancer detected
How is Prostate Cancer Detected?
  • DRE
  • PSA

A combination is best

prostate cancer therapies
Prostate Cancer Therapies
  • Watch and wait
    • Generally a slow-growing cancer
  • Surgery
    • Surgical excision, nerve-sparing (hopefully)
  • Brachiitherapy
    • Implantation of radioactive pellets
a cancer case study
A Cancer Case Study
  • HPI:
    • A 25 yo male athlete presents with severe cough, SOB; c/o a painful R. testicle
  • O/E:
    • Non-encapsulated mass in testes; masses detected in abdomen, lungs and brain
  • Dx:
    • Metastatic testicular cancer (choriocarcinoma, 40% embryonal, 1% teratoma
testicular cancer factoids
Testicular Cancer Factoids
  • Most common cancer in men 15 – 35
  • 90% cure rate if detected early
  • Method of detection:
    • Routine testicular palpation
  • Surgical excision of testicle
  • Surgery to remove 2 cancerous lesions on brain
  • Chemotherapy:
    • 1 round of BEP (bleomycin, etoposide, platinol)
    • 3 rounds of VIP (Ifostamide, etoposide, platinol)
  • Period of treatment:
    • October – December, 1996
lance armstrong
Lance Armstrong
  • 6-time Tour de France winner (AFTER getting cancer)
responsiveness to chemotherapy
These Cancers Respond:

Hodgkins lymphoma



Wilm’s tumor

Testicular, other germ line ca’s

These may respond:

Breast, ovarian, endometrial, myeloma, large intestine, esophageal CA’s

Responsiveness to Chemotherapy
  • These do NOT respond:
    • Thyroid, Brain CA, liver, malignant melanoma, pancreatic, cervical