Cancer Treatment and Chemotherapy Overview

Lecture 8: Anticancer Drugs

• Anticancer drugs are chemotherapeutic agents used to treat cancer.
• Types of anticancer drugs include alkylating agents, antimetabolites, and mitotic inhibitors.

Hallmarks of Cancer

• Rapid uncontrolled cell proliferation
• Malignant transformation
• Loss of function
• Resistance to apoptosis
• Inducing angiogenesis
• Invasion and metastasis
• Avoiding immune destruction

Proliferation, Differentiation, and Undifferentiation

• Cancer cells have a faster doubling time compared to normal cells.
• Cancer cells lose their normal shape and structure.
• Differentiation is lost in cancer cells.

Cell Cycle Regulators

• Positive regulators: growth factors acting on protein kinase receptors
• Negative regulators: P53, BRCA1, BRCA2

Cancer Cell Cycle Kinetics

• Some anticancer drugs act specifically on cycling cells (cell cycle-specific (CCS) drugs).
• Others kill tumor cells in both cycling and resting phases (cell cycle-nonspecific (CCNS) drugs).
• Cycling cells are more sensitive to CCS drugs.

Anticancer Drugs: Mechanism and Action

• Alkylating agents: DNA cross-linking, disrupting DNA function
• Antimetabolites : Interfere with nucleic acid synthesis by mimicking essential natural molecules.
• Antibiotics: Interact with DNA and/or RNA, leading to DNA damage or disruption
• Microtubule inhibitors: Disrupt microtubule formation, affecting cell division
• Hormones & Antagonists: Hormones bind to target cells, causing uncontrolled growth. Antagonist drugs interfere with the hormone effect
• Tyrosine kinase inhibitors: Block enzymes for growth and division
• Monoclonal antibodies (MABs): Bind to specific proteins on cancer cells, inhibiting their growth

Principles of Cancer Chemotherapy

• Cancer chemotherapy aims to cause a lethal cytotoxic event or apoptosis in cancer cells and arrest tumor growth.
• The attack is usually directed toward DNA or against metabolic sites essential for cell replication to block or damage cancer cells.

Treatment Strategies

• The ultimate goal of chemotherapy is a cure (long-term disease-free survival).
• Some tumors are treated for eradication of every neoplastic cell, but others can only be treated to control the disease.

Resistance to Anticancer Drugs

• Increased DNA repair
• Formation of trapping agents
• Changes in target enzymes
• Decreased activation of prodrugs
• Decreased drug accumulation

Adverse Effects of Anticancer Drugs

• Bone marrow toxicity (myelosuppression)
• Impaired wound healing
• Hair loss (alopecia)
• Damage to gastrointestinal (GI) epithelium
• Hepatotoxicity
• Sterility
• Teratogenicity and carcinogenicity

Classes of Anticancer Drugs

• Alkylating agents
• Antimetabolites
• Cytotoxic antibiotics
• Microtubule inhibitors
• Hormone antagonists
• Tyrosine kinase inhibitors
• Monoclonal antibodies
• Miscellaneous agents

1- Alkylating Agents

• Includes nitrogen mustards, nitrosoureas, and platinum compounds
• Mechanism of action is DNA cross-linking.

2- Antimetabolites

• Structurally related to normal compounds found in cells
• Interfere with nucleic acid synthesis

3- Antibiotics

• Cytotoxic action primarily due to their interactions with DNA

4- Microtubule Inhibitors

• Disrupt microtubule formation, affecting cell division

5- Hormones and Their Antagonists

• Some tumors are hormone-dependent (e.g., breast and prostate cancers).
• Hormone antagonists are used in the treatment of these tumors.

6- Tyrosine Kinase Inhibitors

• Tyrosine kinases are involved in cell growth and division.
• These inhibitors block the activity of specific tyrosine kinases.

7- Monoclonal Antibodies

• They are designed to bind to specific protein targets on the surface of cancer cells.

8- Miscellaneous Agents

• Includes agents like Bortezomib and Interferons
• Act through various mechanisms to attack tumors.