Pharmacology - CANCER DRUGS - HORMONAL THERAPY (MADE EASY)

Summary

This lecture covers the pharmacology of anticancer enzymes and hormonal therapies used in cancer treatment. It explains the process of cancer development, cell cycle regulation, and how cancer cells evade normal controls. The script details various drugs targeting specific cell cycle phases, such as Asparaginase for leukemia and aromatase inhibitors for breast cancer. It also discusses hormonal therapies like GnRH agonists for prostate cancer and antiandrogens for hormone-sensitive cancers. The video further covers potential side effects of these treatments, offering insights into their use and effectiveness in managing cancer.

Takeaways

• 😀 Cancer is characterized by the uncontrolled growth of abnormal cells that bypass the normal cell cycle checkpoints.
• 😀 The cell cycle consists of phases: G1 (growth), S (DNA replication), G2 (preparation for division), and M (mitosis), with specific checkpoints ensuring correct progression.
• 😀 Chemotherapy drugs can be cell cycle-specific (targeting specific phases) or cell cycle-nonspecific (affecting any phase).
• 😀 Asparaginase is used to treat leukemia by breaking down asparagine, depriving cancer cells of essential proteins, leading to cell cycle arrest and apoptosis.
• 😀 Pegaspargase, a modified version of Asparaginase, has a longer duration of action and fewer allergic reactions.
• 😀 Estrogen promotes cell proliferation, particularly in hormone-sensitive cancers like breast cancer, through estrogen receptors (ER).
• 😀 Aromatase inhibitors (e.g., Anastrozole, Letrozole) block the enzyme aromatase, reducing estrogen levels in postmenopausal women and limiting cancer cell growth.
• 😀 Selective Estrogen Receptor Modulators (SERMs) like Tamoxifen block estrogen from binding to its receptor, preventing estrogen-driven cancer cell growth.
• 😀 GnRH agonists like Leuprolide and Goserelin suppress ovarian estrogen production by overstimulating GnRH receptors, while GnRH antagonists (e.g., Degarelix) avoid initial hormone surges.
• 😀 In prostate cancer, testosterone promotes growth via conversion to DHT. Antiandrogens (e.g., Flutamide, Bicalutamide) block androgen receptors to reduce cancer cell growth.
• 😀 Abiraterone inhibits CYP17A1, disrupting testosterone synthesis in prostate cancer, leading to reduced androgen levels and cancer cell shrinkage.

Q & A

What is cancer, and how does it develop?

Cancer is defined as the uncontrolled growth of abnormal cells in the body. While normal cell growth is regulated, cancer cells evade the controls that regulate cell proliferation and survival, leading to their unchecked growth.

Can you explain the cell cycle and its phases?

The cell cycle consists of several phases: G1 (growth and preparation for DNA replication), S (synthesis phase where DNA replication occurs), G2 (second gap phase for continued growth and preparation for division), and M (mitosis, where cell division occurs). After the M phase, cells either exit the cycle into the G0 phase or return to G1 for further division.

What are the main checkpoints in the cell cycle?

The main checkpoints in the cell cycle are the G1 checkpoint, G2 checkpoint, and M checkpoint. These checkpoints ensure each phase is completed correctly before the cell proceeds to the next stage.

How do chemotherapy agents target cancer cells in relation to the cell cycle?

Chemotherapy agents target fast-dividing cells at different phases of the cell cycle. Drugs that are cytotoxic during specific phases are called cell cycle-specific drugs, while those cytotoxic in any phase are called cell cycle-nonspecific drugs.

How does Asparaginase work in treating leukemia?

Asparaginase is an enzyme that breaks down asparagine, a vital amino acid for protein synthesis. Some leukemia cells lack the enzyme to produce asparagine and depend on an external supply. Asparaginase depletes asparagine, inhibiting protein synthesis and causing cell cycle arrest and apoptosis in leukemia cells.

What are the main approaches to interrupt estrogen-dependent cancer processes?

There are four main methods to interrupt estrogen-dependent processes: (1) inhibit estrogen production using aromatase inhibitors, (2) prevent estrogen from binding to its receptor using selective estrogen receptor modulators (SERMs), (3) reduce estrogen receptor expression with selective estrogen receptor down-regulators, and (4) suppress ovarian estrogen production with GnRH agonists.

What are aromatase inhibitors, and how do they work in cancer treatment?

Aromatase inhibitors, such as Anastrozole, Letrozole, and Exemestane, block the aromatase enzyme, which is responsible for converting androstenedione and testosterone into estrogens. This reduces estrogen production, especially in postmenopausal women, thereby inhibiting estrogen-driven cancer growth.

How do selective estrogen receptor modulators (SERMs) work?

SERMs, like Tamoxifen and Raloxifene, bind to estrogen receptors and adopt a different conformation than estrogen. This prevents the estrogen-receptor complex from activating genes that promote cancer cell growth, effectively blocking estrogen’s growth-promoting effects.

What is the role of GnRH agonists in cancer treatment?

GnRH agonists, such as Leuprolide and Goserelin, overstimulate GnRH receptors on the pituitary gland, leading to desensitization. This reduces the secretion of LH and FSH, lowering estrogen production in women and testosterone in men, which can be used in the treatment of hormone-sensitive cancers like breast and prostate cancer.

What are the potential side effects of Asparaginase, aromatase inhibitors, and GnRH agonists?

Asparaginase and Pegaspargase can cause fatigue, poor appetite, mouth sores, pancreatitis, and blood clots. Aromatase inhibitors and GnRH agonists can lead to fatigue, muscle and joint pain, hot flashes, and osteoporosis. SERMs can cause blood clots, stroke, and endometrial cancer, while antiandrogens in men may cause breast enlargement, hot flashes, sexual dysfunction, and osteoporosis.