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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

Drugs Used in the treatment of Cancer

Pharmacology 49.222

Bill Diehl-Jones RN, PhD

Faculty of Nursing and Department of Zoology

agenda
Agenda
  • 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)

STOP

Inhibitors of

DNA Function

(Doxorubicin, Cisplatin)

STOP

STOP

Inhibitors of

DNA Replication

(Cytochalasin, Vincristine)

Protein

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

mechanisms

Metabolites

Free Radicals

Mechanisms

Estrogen/Estrogen-like Molecules

Induce Cell-Proliferation Genes

Estrogen/Estrogen-Like Metabolites

Form DNA Mutations

OH•, O•

dna adducts why are they problematic

G

G

C

C

A

T

T

G

C

A

A

T

T

T

A

A

T

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:

Exogenous

Estrogen

Androstenedione

Testosterone

AI

Aromatase

Estrone

Estradiol

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
treatment
Treatment
  • 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

ALL

Choriocarcinoma

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