Chemotherapy Treatment Options and History

Chemotherapy Treatment Options

• Chemotherapy uses chemical agents (natural, semi-synthetic, or synthetic) to destroy or control cancer cell growth.
• Chemotherapy can treat cancer cells that have escaped the primary tumor because it treats the whole body.
• Current methods include surgery (for localized tumors), radiation therapy (for localized tumors), and chemotherapy (for disseminated tumors).

History of Chemotherapy

• The concept of a "magic bullet" (a targeted toxin) was introduced by Paul Ehrlich.
• Modern chemotherapy began during World War I with exposure to mustard gas, which destroyed bone marrow, leading to DNA alkylation and apoptosis.
• Alfred Gilman and Louis Goodman showed mustard agents' therapeutic benefits in treating lymphoma in the 1940s.
• Combination therapy became popular in the 1960s, leading to improved survival rates in childhood leukemia.

Modern Chemotherapies

• Early treatments used 5-fluorouracil for solid tumors.
• Combination therapies are now routine, such as FOLFOX (for bowel cancer) and FOLFIRI (for colorectal cancer).

Chemotherapy Mechanisms

• Cytotoxic chemotherapy disrupts cell cycle processes, primarily targeting tumor cells at the cellular level.
• These drugs interfere with DNA synthesis and mitotic processes, particularly the S and M phases.
• They do not distinguish between normal and cancer cells, causing adverse reactions.

Issues with Chemotherapy

• Chemotherapy primarily targets rapidly dividing cells.
• This includes bone marrow, gastrointestinal tract, and hair follicles.
• Common toxicities include myelosuppression (neutropenia, anemia, thrombocytopenia), increased infection risk, nausea, vomiting, diarrhea, mucositis (inflammation of digestive lining), alopecia, and various organ toxicities (kidneys, heart, etc.).

Different Chemotherapy Approaches

• Alkylating agents (e.g., Cisplatin):
  • Binds to DNA, causing DNA lesions and impairing replication.
  • Causes significant side effects like nephrotoxicity (kidney damage), hepatotoxicity (liver damage), and gastrointestinal problems.
• Antimetabolites (e.g., Methotrexate):
  • Interfere with folic acid metabolism, thus impacting DNA synthesis and repair.
  • Common side effects include renal, hepatic, pulmonary, and neurotoxicity (affecting kidneys, liver, lungs, and nervous system).
• Topoisomerase Inhibitors (e.g., Topotecan, Doxorubicin):
  • Topotecan interrupts DNA's supercoiling, causing single-strand breaks.
  • Doxorubicin inhibits topoisomerase II, affecting DNA replication and repair with a serious side effect being cardiotoxicity (damage to the heart)
• Microtubule Poisons (e.g., Vincristine):
  • Disrupts microtubule formation, interfering with cell division.
  • Side effects include cardiac, gastrointestinal, and central nervous system (CNS) issues.

Explore the various chemotherapy treatment options, including historical developments that led to modern practices. Learn about key figures in chemotherapy, such as Paul Ehrlich, and the significance of combination therapies in improving cancer survival rates.