In Depth Notes on Cancer Chemotherapy CPPS 307

Definition of Cancer: Cancer is characterized by abnormally proliferating cells that can infiltrate and destroy normal tissues.
Key Mechanism: Tumorigenic mutations disrupt the stability of the cell cycle, leading to unchecked proliferation.
- Sources of Mutations:
- Errors in DNA replication/mistakes during mitosis.
- Mutations in checkpoint and tumor suppressor genes (e.g., p53, BRCA1).

Metabolic Changes: The Warburg effect signifies preferential anaerobic metabolism of glucose.
Genetic Alterations:
- Generation of oncogenes (e.g., Ras, Myc).
- Inactivation of tumor suppressor genes (e.g., p53, PTEN, Rb1).
- Inactivation of DNA repair genes.
Telomere Dynamics:
- Telomeres protect chromosome ends from degradation.
- Telomere shortening leads to the Hayflick limit, denoting a cell's limited division potential.
- Cancer cells often express telomerase, preserving telomere length and allowing unlimited replication.

Diagnosis Methods:
- Clinical Assessment: Initial examination and patient history.
- Imaging Techniques:
- Ultrasound, MRI, and PET scans are commonly used for detecting tumors.
- Histopathology: Tissue biopsies stained with hematoxylin and eosin to identify cancerous cells.
TNM Classification System:
- T: Size of Tumor
- N: Lymph Node involvement
- M: Metastasis status

General Treatment Categories:
- Systemic Treatments:
- Cytotoxic Chemotherapy.
- Targeted therapies like hormone therapy, immunotherapy, and molecular targeted therapy.
Indications for Chemotherapy:
- Curative Therapy: Example includes lymphoma treatment.
- Disease Control: Used when tumors are not surgically removable or have metastasized.
- Neoadjuvant Therapy: Given to shrink tumors before surgery.
- Adjuvant Chemotherapy: Administered post-surgery to eliminate residual cancer cells.
Basic Principles:
- Aim to destroy cancer cells while minimizing harm to normal ones.
- Multiple doses required due to cell killing being non-complete after a single dose.
- Treatment intervals are critical for recovery of normal cells.
- Combination therapies improve overall efficacy by targeting multiple pathways and reducing side effects.

Major Challenges:
- Unacceptable Side Effects:
- Myelosuppression (leukopenia and thrombocytopenia).
- Gastrointestinal toxicity (mucositis, diarrhea).
- Hair loss (alopecia).
- Peripheral neuropathy.
- Development of Resistance:
- Cancer cells may develop mechanisms to resist chemotherapy, including mechanisms such as increased efflux of drugs through P-glycoprotein, decreased uptake, metabolic inactivation, and increased DNA repair capabilities.

Increased Drug Efflux:
- MDR1 gene leads to greater efflux of anticancer agents like Vincristine and Doxorubicin.
Decreased Drug Uptake:
- Examples include decreased intake of Methotrexate.
Metabolic Inactivation:
- Such as increased aldehyde dehydrogenase activity inactivated Cyclophosphamide.
Target Amplification:
- Overproduction of target enzymes that lead to resistance, e.g., increased dihydrofolate reductase in Methotrexate resistance.

Which guideline is for combination chemotherapy design?
- A) Use drugs active orally.
- B) Use drugs that target the same molecular target.
- C) Use drugs with minimal overlapping toxicity.
- D) Use drugs with the same molecular mass.
- E) Use drugs metabolized the same route.
What is the term for chemotherapy given after surgery?
- A) Adjuvant therapy
- B) Curative therapy
- C) Elective therapy
- D) Palliative therapy
Primary goals for chemotherapy may include:
- A) Reducing tumor burden.
- B) Adjunctive therapy post-surgery.
- C) Achieving complete remission.
- D) All of the above.