Cytostatics, classification

Substances from different classes of active ingredients, which have an antineoplastic effect. In a narrower sense, the term "cytostatic drugs" is used to describe conventional non-selective cytostatic drugs which use a broad spectrum of non-selective substances to inhibit the growth of proliferating cells, i.e. tumour cells, but also of healthy cells with a high proliferation rate (see also antineoplastic tumour therapeutics).

Conventional cytostatics (non-specific/ non-selective cytotoxic on proliferating, thus on tumor cells but also on healthy cells effective chemotherapeutic agents)

• Antimetabolites
• Alkylating cytostatics
• Topoisomerase inhibitors
• Mitosis inhibitors
• Cytostatically active antimetabolites
• Other
  • asparaginase, hydroxyurea, radium-223-dichloride

Classification according to substance groups and substances:

Antimetabolites

• Folic acid analogues
  • Methotrexate
  • Pemetrexed
• Purine analogues
  • 6-mercaptopurine
  • Pentostatin
  • Cladribine
• Pyrimidine analogues
  • 5-fluorouracil
  • Capecitabine
  • Gemcitabine

Alkylating cytostatic drugs

• Nitrogen-lost derivatives
  • Cyclophosphamide
  • Trofosfamide
  • Ifosfamide
  • Chlorambucil
  • Melphalan
• Nitrosoureas
  • Carmustine (BCNU)
  • Lomustine (CCNU)
• Platinum compounds

  • Carboplatin

  • Oxaliplatin

• Other alkylating substances ◦Procarbazine
  • Temozolomide

Topoisomerase inhibitor

• Topotecan
• Irinotecan
• Etoposide (inhibitor of topoisomerase II)
• Teniposide

Mitosis inhibitor

• Vinca alkaloids
  • Vinblastine
  • Vincristine
• Taxanes
  • Paclitaxel
  • Docetaxel
  • Cabazitaxel

Cytostatic antibiotics

• Daunorubicin
• Doxorubicin
• Bleomycin

Other cytostatic drugs

• Asparaginase
• Hydroxyurea
• Radium-223-dichloride

The cell cycle always follows the same pattern in tumour cells. It consists of

• Mitosis (nuclear or cell division)
• Interphase (G1-S-G2 phase
• Rest phase (G0 phase).

Tumour cells can also move from the G1 phase into the G0 phase (resting phase) and return to the G1 phase after stimulation by growth factors. In the G0 phase, tumour cells are not very sensitive to most cytostatic drugs.

The cell cycle is checked for errors at checkpoints during the transition from the G1 phase to the S phase and from the G2 phase to the M phase. If DNA damage is detected at the end of the G1 phase, either DNA repair or, in the case of irreparable damage, apoptosis occurs. The checkpoints are controlled by cyclins and cycline-dependent kinases (CDK), which are activated by proto-oncogenes or their products. Protooncogenes are genes of normal cells that code for proteins involved in cell growth (growth promoting).

These include:

• growth factors e.g. EGF, VEGF
• Growth factor receptors e.g. EGFR, VEGR, IGFR
• Kinases involved in signal transduction, e.g. RAF (serine-threonine kinase) or mTOR
• DNA binding proteins, e.g. MYC, FOS, MYB

In addition to protooncogenes, tumour suppressor genes (coding for growth-inhibiting proteins) also play an important role at the checkpoints, according to the product of the tumour suppressor gene p53. The p53 protein is a transcription factor that initiates cell cycle arrest or targeted apoptosis (apoptosis gene).

Tumour genesis: In general, the control mechanisms at the checkpoints no longer function, so that the balance between cell growth and cell death is shifted in favour of cell growth. Mutations of proto-oncogenes result in oncogenes that stimulate cell growth uninhibited. If additional mutations occur in the tumour suppressor genes (frequently mutated p53), further copying errors occur in the next cell cycles. The cell cycle is no longer stopped due to the lack of control mechanisms at the checkpoints. The tumour cells grow unhindered.