AntiCancer - I

There are three treatment possibilities for cancer: surgery, radiotherapy, and chemotherapy. This lecture will address chemotherapy and some cancer basics.

Cancer Stats:

1. > 1 million people are diagnosed with cancer in the US each year.

2. 550,000 deaths occur due to cancer each year. That’s one person every 62 seconds.

3. Cancer is the second most frequent cause of death in the US. (Heart disease is #1.)

4. Cancer is the leading cause of death in women between the ages of 30-74. The most common causes of cancer in women are breast, lung, and colorectal.

5. The most common causes of cancer in men are prostate, lung, and colorectal.

6. Cancer is the main non-accidental cause of death in children 1-14 years old. 76,000 children die each year from cancer.

History of Cancer Chemotherapeutics:

We’ve come a long way...

decade	Five year survival
1930’s	20 %
1940’s	25 %
1960’s	33 %
1990’s	50 %

The paper describing Nitrogen Mustards was published in 1946 by Goodman, Gilman, and some other folks, and it is regarded as the beginning of cancer chemotherapy. The story of first patient treated with Nitrogen Mustard demonstrates certain problems with chemotherapy that we are still dealing with today - only a certain amount of the drug can be tolerated and resistance often develops. This patient had terminal stage lymphosarcoma with big mediastinal and axillary masses that made breathing, chewing, and swallowing difficult. 2 days after treatment started, there was softening of the tumor tissue. In 4 days his obstructive difficulties were ameliorated. But in 3 ½ weeks his white blood cell count dropped to 200 cells/ml, and the treatment had to be stopped. The tumor grew again, so a second course of treatment was started. This course gave a transient improvement, but also had to be stopped when the patient could no longer tolerate it. A third course of chemo showed no improvement at all.

Causes of Cancer:

1. 30 % is due to smoking: lung, mouth, pharynx, larynx, esophagus, urinary bladder, pancreas, and kidney.

2. Lifestyle – diet, alcohol consumption, reproductive behavior, sexual behavior, exposure to sunlight, etc.

3. These are the only ones she listed, so I guess these are the only causes that exist... Right?

Characteristics of Tumors:

1. Benign – we are not going to talk about these ones.

2. Malignant – Malignant tumors metastasize via direct extension, via lymphatic routes or via blood. It is important to know the methods of metastasis of a given cancer so you can treat both the primary location and the locations to which the cancer has spread.

Hallmarks of cancer cells:

1. Persistent cell proliferation

2. Invasive growth

3. Metastasis

Etiology of cancer:

Genomic instability and loss of regulatory proteins (e.g. p53) contribute to the immortalization of cell lines. DNA is altered via mutagens including chemical carcinogens, viruses, and radiation. The mutations cause by these mutagens lead to activation of oncogenes and inactivation of tumor suppressor genes.

Growth Fraction:

1. Growth Fraction = _____# of proliferating cells____

# of cells in Go phase of cell cycle

2. Cells with a high growth fraction are cells that are frequently proliferating. These include:

• Epithelial cells

• Bone marrow cells

• Hair follicle cells

• Sperm cells

3. Chemotherapeutic drugs tend to work in all phases of the cell cycle except for Go, the resting phase.

4. Growth fraction has an impact on the ability of chemotherapy to effectively treat a given cancer. For example, solid tumors characteristically have a low growth fraction, and this contributes to their poor response to chemotherapy.

5. Leukemia, a disseminated tumor, has a high growth fraction, and it often responds very well to chemo therapy.

Recruitment:

The response of a solid tumor to chemotherapy can be improved through recruitment, a process which increases the growth fraction of a tumor. When you have a big tumor, it may out grow its blood supply to a certain extent and be under-nourished. This causes many of the cells to be in the resting phase. In recruitment, you initially reduce the size of the tumor via irradiation therapy or surgery. This induces the remaining tumor cells to re-enter the G1 phase of the cell cycle, and increases the number of proliferating cells. This improves the tumor response to chemotherapy.

Cancers where chemotherapy works very well:

• Childhood leukemia

• Wilm’s Tumor

• Retinoblastoma

• Rhabdomyosarcoma

• Ewing’s Sarcoma

• Osteosarcoma

• Testicular Cancer

• Choriocarcinoma in women

• Hodgkin’s Disease

• Some lymphomas

• Some early breast cancers

Cancers that are very difficult to treat with chemotherapeutics:

• Colon

• Lung

• Late stage breast cancer

• Pancreatic cancer

Category: Pharmacology Notes