Rehab Essentials Part 16: Cancer Chemotherapy

What is the goal of cancer chemotherapy?

Selective toxicity of neoplastic cells

What are primary methods of cancer chemotherapy? (2)

1. Disrupt DNA/RNA function

2. Inhibit mitosis and initiate cell death

What are the functional drug groups for chemotherapy?

1. Direct effect on DNA

2. Direct effect on mitosis

3. Hormones

4. Targeted therapies

5. Immunothearpies

6. Miscellaneous

What are drugs that affects DNA synthesis and function?

1. Alkylating agents

2. Antitumor antibiotics

3. Platinum drugs

4. Topoisomerase inhibitors

5. Antimetabolites

What do alkylating agents do?

1. Bind strongly to DNA bases

2. Form cross-link within/between DNA strands

What does alkylating agents forming cross-links between DNA strands ultimately do?

1. Prevent DNA replication/translation

2. Cause breaks in DNA chain

What are examples of alkylating agents?

What are antitumor antibiotics?

Antibacterials that are reserves for cancer because of toxicitiy

What do antitumor antibiotics do as they are inserted into DNA strand?

1. Inhibit transcription

2. Cause breaks in DNA chain

What are examples of antitumor antibiotics?

What are platinum coordination complexes?

Drugs that contain platinum and form strong cross-links in DNA, inhibiting replicatoin

What are examples of platinum coordination complexes?

What is topoisomerase?

Key enzymes needed for DNA replicaiton

What are topoisomerase inhibitors?

Drugs that inhibit the enzyme, causing breaks in DNA chain

What are the two types of topoisomerase inhibitors?

Type I

Type II

What do antimetabolites do?

Act on pathways for DNA synthesis to impair DNA synthesis

How do antimetabolites impair DNA synthesis?

1. Inhibit enzymes

2. Act as bogus ingredients

What are examples of antimetabolites?

How do anti-cancer drugs directly effect DNA synthesis and function?

1. By binding strongly to DNA

2. INhibiting DNA enzymes

3. Inhibiting steps in DNA/RNA synthesis

What drugs bind strongly to DNA? (3)

1. Alkylating agents

2. Antitumor antibiotics

3. Platinum drugs

What drugs inhibit DNA enzymes?

Topoisomerase inhibitors

What drugs inhibit steps in DNA/RNA synthesis?

Antimetabolites

What do drugs affecting DNA synthesis/function cause?

Severe/toxic side effects because they do not discriminate between cancer cells and healthy cells

What are drugs that directly inhibit mitosis?

Antimicrotubule agents

What are microtubules?

Located in mitotic apparatus, and must function properly during cell division

What can certain drugs affect?

Microtubules, impairing cell division

What are the types of antimicrotubule agents?

1. Vinka alkaloids

2. TAxanes

What do vinka alkaloids do?

Inhibit formation of microtubules

What do taxanes do?

Inhibit breakdown of microtubules

What are examples of vinka alkaloids?

What are examples of taxanes?

What do anticancer hormones act on?

Hormone-sensitive cancers

What are anticancer hormones used to do?

1. Inhibit production of a hormone

2. Block or reduce effects of a hormone

3. Inhibit cell growth or induce growth in certain cells

What drugs inhibit production of a hormone?

Aromatase inhibitors in breast cancer

What drugs block or reduce effects of a hormone?

Androgen receptor blockers in prostate cancer

What drugs inhibit cell growth or induce death in certain cells?

Prednisone in leukemia, lymphoma

Why do conventional anticancer drugs often cause severe side effects?

Most of these drugs do not discriminate between healthy tissues and cancerous cells

What do conventional anti-cancer drugs do?

Decrease mitosis in cancer and healthy cells

What do targeted therapies do?

Focus on a specific abnormal trait in the cancer cell that is not present in healthy cells

What are primary targeted therapies?

1. Monoclonal antibodies

2. Tyrosine kinase inhibitors

What are monoclonal antibodies (MABs) derived from?

Cell cloning techniques used to manufacture antibodies that bind to a specific antigen on tumor cells..."targeting" effect

Can MABs have direct effect on cancer cells?

Yes

What can MABs do after binding to an antigen?

1. Block signaling pathways that cause mitosis

2. Initiate programmed cell death (apoptosis)

3. Inhibit angiogenesis

What are examples of MABs for specific cancers?

What is tyrosine kinase?

Receptor/enzyme on cell surface that signals the cell to divide

What happens to tyrosine kinase in cancer cells?

Malfunctioning or too many of them; or causing them to divide too much

What do certain cancers have?

Abnormal tyrosine kinases (ex. HER2, ErbB-1)

What does activiation of these abnormal tyrosine kinases cause?

Uncontrolled cell proliferation

What do tyrosine kinase inhibitors do? (2)

1. Bind to tyrosine kinase site, inhibiting receptor activation

2. Prevents receptor from initiating signals that cause cell division

What are examples of tyrosine kinase inhibitors?

What do drugs that impair microtubule function do?

Directly inhibit mitosis

What are specific hormones used in?

Hormone sensitive cancers to decrease cell proliferation

What do targeted treatments allow?

Anti-cancer drug to more selectively affect cancer cells with fewer toxic effects on healthy cells

What do immunotherapies encourage?

Body's immune system to deal with cancer system (aka. biological therapies)

What are examples of immunotherapies?

1. Cytokines

2. MABs

3. Others

What are cytokines?

Small proteins that plan an important role in immune responses

What are the two primary strategies of cytokines?

1. Interferons (INF alpha 2b)

2. Interleukins (IL-2)

What are the effects of cytokines?

1. Directly activate pathways that inhibit cell division, promote cell death

2. Encourage cytotoxic immune cells (T lymph, NK cells) to attack cancer cells

What do some MABs do?

Sensitize cancer cell to attack from T lymphocytes

What do some other monoclonal antibodies do?

They inhibit proteins that are suppressing the immune cells that normally attack cancer "checkpoint inhibitors"; different than targeted therapies

What are some examples of other immunotherapies?

1. Anticancer vaccines (HPV, Hep B)

2. Adoptive cell transfer (grow pt's T cells in lab, reinsert into patient)

3. Modify and engineer T cells to attack specific cancers (could get really sick)

What do some miscellaneous agents do?

Generally disrupt DNA structure or cancer cell metabolism

What does asparaginase do?

Deprive tumor cells of asparagine

What do histone deacetylase inhibitors do?

Affect proteins that package DNA in a cell

What do retinoids do?

Enhance cell differentiation

What is the combination of chemotherapy agents ABVD used for?

Hodgkin lymphoma

What is the combination of chemotherapy agents CMF used for?

Early stage breast cancer

What is the combination of chemotherapy agents FOLFOX used for?

Colorectal cancer

What are side effects of chemotherapy?

1. Hair loss

2. GI problems

3. Anemia

4. Fatigue

5. Neurotoxicity

6. Cardiotoxicity

7. Skin rashes

8. Others

What are side effects of chemotherapy caused by?

Inhibiting cell replication

What have newer targeted therapies caused?

Less side effects

What are some rehab concerns for those in cancer treatment/

1. Pain support, help manage pain

2. Exercise

How does exercise play a role in cancer treatment?

Exercise should occur before, during, after chemo to increase strength, ROM, CV function as indicated/tolerated

What is the overall success of cancer chemotherapy?

Decreased cancer mortality over last 30 years

What are some current issues with cancer therapy? (2)

1. Success is limited in certain cancers (lung, pancreatic)

2. Drug resistance

What are some future perspectives of cancer therapy? (4)

1. More, better targeted therapies

2. More vaccines

3. Drugs that protect healthy cells from chemo drugs

4. Personalized oncology

What is personalized oncology?

Tailoring treatment based on characteristics of tumor in each individual

What remains one of the best anti-cancer strategies?

Prevention

What are some strategies that can help prevent cancer?

1. Regular exercise

2. Quit smoking

3. Eat a low-fat, high fiber diet

4. Use sunscreen, and avoid excessive UV exposure

5. Early detection regular screens

What do certain anti-cancer drugs to?

Activate or mimic the immune system's ability to find and kill cancer cells

What role should PTs have in cancer treatment?

Make their patients aware of ways to prevent cancer, and screening techniques that should be used for early detection of cancer