Chemotherapy

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Malignancy occurs when cells mutate to replicate uncontrollably, outside of the body's normal control mechanisms and immune response, and gains the ability to invade into other tissues.

Cell cycle



As cancer cells tend to replicate faster than other cells, chemotherapy primarily affects cancer cells by affecting their replication.



Types of Chemotherapy
Chemotherapies work in several ways. They either target all cells, cells which are in certain phases of cell replication, or some newer therapies and therapies being developed targets cancer cells specifically.

Cross linkers 
  • Work by forming  bonds between base pairs in DNA strands 
  • Also forms breaks in DNA's sugar backbone
  • This stops the cell from being able to synthesise DNA and therefore replicate
  • Given as a single bolus
Includes:
  • Alkylating agents eg. Cyclophosphamide
  • Platinum eg. Cisplatin, Carboplatin. 
Antimetabolites
  • Mimics base pairs or blocks their production. 
  • Act in cells undergoing DNA replication to block replication. (S phase)
  • Requires longer infusion time as it only works in S phase and therefore only kills the cells which are in S phase at the time the drug is present. 
Includes:
  • 5 Fluorouracil
  • Cytarabine
  • Methotrexate
  • 6 mercaptopurine
Topoisomerase inhibitors
  • Inhibits topoisomerase which is an enzyme which unwinds DNA
  • Also works in S phase
  • Requires longer infusion times
Includes: 
Topo I inhibitors eg. irinotecan, topotecan
Topo II inhibitors eg. etoposide, teniposide

DNA intercalators 
  • work by sitting between DNA molecules affecting their structure and therefore stops replication
Includes 
  • doxorubicin
  • epirubicin

Tubule toxins
  • Disrupts microtubules in M phase
  • Longer infusion also needed as it only affects cells replicating. 
Includes: 
  • Vinca-alkaloids eg. Vincristine
  • Taxanes eg. paclitaxel
Many chemotherapy agents are not specific to cancer cells, and affect other cells as well. Some cells replicate slowly, and are less likely to be affected by chemotherapeutic agents. On the other hand, cells with a quick turnover rate in the body are often affected at the same time as cancer cells. These include cells in the gut lining, the bone marrow, and skin and hair cells. This is why chemotherapy often has many side effects, which worsens as a patient undergoes more cycles. Some side effects include: hair loss, brittle nails (due to effects on skin cells), neutropenia, bruising (due to effects on bone marrow), and vomiting, nausea, and diarrhoea (due to effects on the gut)


Chemotherapy may be used curatively (often as combinations), as adjuvant or neoadjuvant with other therapy such as surgery or radiotherapy, or palliatively (usually single agent) to reduce the size of the cancer for symptomatic relief or a survival benefit.

Targeted therapy

There have been an increase in new targeted therapies for cancer patients. These are primarily antibodies which binds with receptors on specific cancer cells, or ligands which act on these receptors, to stop replication. These antibodies may also be joined to a cytotoxic agent or radioactive agents, therefore delivering these agents specifically to the cancer cells. Some act by inhibiting tyrosine kinase, a enzyme which catalyses a cascade of reaction which leads to replication. Examples of targeted therapies include Herceptin, used to treat certain breast cancers, and epiluminab, which is not licensed, but may be used to treat metastatic melanoma.

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