Biology 207 Spring 2004

Biology of Cancer

Lecture 21 and 22: “Cancer Treatments”

Readings: King Chap. 13; Breast cancer microarrays (figures):

http://genome-www.stanford.edu/breast_cancer/sbcmp/figures.shtml from article by Perou et al. (1999) Proceedings of the National Academy of Sciences 96:9212-9217 available from JSTOR, Milne library.

Outline:

1. Overview of cancer treatments

2. Cancer specific and stage-specific treatments

3. Advances: surgery, radiation treatments

4. Chemotherapy

5. Individualized treatments/microarrays

Lecture: “Cancer Treatments”

1. Overview of cancer treatments

Major treatment approaches

· surgery

· radiation therapy

· chemotherapy

· bone marrow transplant

· hormone therapy

Cancer in situ:

surgery, follow-up radiation or chemotherapy?

Larger in situ tumors:

surgery + radiation or chemotherapy

Metastatic cancer:

surgery + chemotherapy

2. Cancer-specific and stage-specific treatments

Rationale:

Each cancer type is different and may respond to different treatments; cancer is diagnosed at various stages in different individuals. Thus, it makes sense to have different treatment options for each cancer.

examples:

bone marrow transplant: leukemias

radiation: cervical, esophageal, oral cancers

chemotherapy: Burkitt’s lymphoma, Hodgkin’s lymphoma, Acute Lymphocytic Leukemia, testicular cancer

hormone-based treatments: organs that produce or receive hormonal signals:

tamoxifen (anti-estrogen)--breast cancer;

anti-androgen therapies--prostate cancer

3. Advances: surgery, radiation treatments

Advances in surgery

· better imaging to locate tumors

· less drastic surgeries: lumpectomy

· reconstruction

· new ways to determine if cancer was removed

· shrink tumors before surgery

Advances in radiation treatments

· specialized machines

· treat localized regions

· implant options

· localized treatment reduces toxic side effects

· different particles used in treatments

· better calculations of radiation doses received by tissues

4. Chemotherapy

Questions/Issues to be considered:

· How do chemotherapeutic drugs work (major classes)?

· Toxicity/side effects

· Drug resistance

· Combination therapies

· Sources of new drugs

· Drug testing/clinical trials

MAJOR CLASSES OF CHEMOTHERAPEUTIC DRUGS

1. Antimetabolites interfere with DNA synthesis.

examples: Methotrexate, fluorouracil, hydroxyurea

2. DNA damaging agents:

--alkylating agents

--inhibitors of DNA enzymes

examples: nitrogen mustard, cisplatin, etoposide

3. Plant products that disrupt cell division

examples: vinblastine, taxol

How do these drugs kill the cancer cells?

· By “starving” them of raw materials for copying DNA.

· OR 2. By damaging their DNA (or not repairing damage) and triggering apoptosis (cell death).

· OR 3. By halting cell division.

Why don’t the drugs kill normal cells?

· Most normal cells don’t divide frequently.

· Normal cells that divide frequently are subject to the chemicals, esp. blood cells, intestinal epithelial cells

· Toxic side effects due to killing of these normal cells

intestinal cells: nausea, vomiting, diarrhea

blood cells: anemia, lack of blood clotting, immunosuppression

Thus drug doses constantly adjusted to balance cancer cell killing and toxicity.

Drug resistance--When cancer cells become altered so they no longer respond to the drug.

Combination therapies--Use of two or three different drugs at the same time to minimize the likelihood of drug resistance.

Adjuvant chemotherapy--Refers to situations when chemotherapy is used along with some other therapy (surgery or radiation therapy)

Screening for new drugs

5. Individualized treatments/microarrays

Pretesting tumors for drugs

Microarray technologies

Biology 207 Spring 2004