DefinitionThis section has been translated automatically.
Antineoplastic tumor therapeutics are substances that inhibit cell growth or cell division. Basically a distinction is made between:
Conventional cytostatics (non-specific/non-selective and thus cytotoxic to proliferating chemotherapeutic agents which act on tumour cells but also on healthy cells)
- Alkylating cytostatics
- Topoisomerase inhibitors
- Mitosis inhibitors
- Cytostatically active antimetabolites
- Asparaginase, hydroxyurea, radium-223 dichloride
tumour therapeutics that are specifically targeted against tumour-specific properties:
ClassificationThis section has been translated automatically.
- Folic acid analogues
- Purine analogues
- Pyrimidine analogues
- Nitrogen Lost Derivatives
- Platinum compounds
- Other alkylating substances
- Etoposide (inhibitor of topoisomerase II)
- Teniposide (topoisomerase II inhibitor)
Cytostatically effective antibiotics
Other cytostatic drugs
- radium-223 dichloride
tumour therapeutics which are specifically directed against tumour-specific properties (e.g. receptors):
- Bevacizumab (VEGF antibody)
- Cetuximab (antibodies against human epidermal growth factors, HER1-4 )
- Trastuzumab (antibodies against human epidermal growth factors, HER1-4 )
- Pertuzumab (antibodies against human epidermal growth factors, HER1-4 )
- Panitumumab (antibodies against human epidermal growth factors, HER1-4 )
- Alemtuzumab (CD52 antibody)
Rituximab (CD20 antibody
)20Y-Ibritumomomab-Tiuxetan(CD20 antibody coupled to the beta emitter 20Y)
- Catamaxomab (antibodies against EpCAM, CD3 and Fc receptors)
- Brentuximab Vedotin (CD30 antibody coupled to the cytostatic spindle poison monomethyl auristatin)
- Nivolumab (checkpoint inhibitor that binds to the immune checkpoint receptor PD-1 (programmed cell death protein)
- Tyrosine kinase inhibitors of the "small molecule immuno-oncology agents" type (kinase inhibitors of the receptors of BCR- ABL, PDGFR, VEGFR, c-Kit, EGFR)
Hormones and hormone antagonists
Substances with anti-oestrogenic effect (breast carcinoma)
Substances with antiandrogenic effect (prostate carcinoma)
Adrogen receptor antagonists (1st and 2nd generation)
- Flutamid (1st generation)
Apalutamide (2nd generation)
Androgen biosynthesis inhibitors
Gonadorelin receptor agonists (Gondorelin = gonadotropin-releasing hormone)
Gonadorelin receptor antagonists (Gondorelin = gonadotropin-releasing hormone)
You might also be interested in
Pharmacodynamics (Effect)This section has been translated automatically.
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.
Field of application/useThis section has been translated automatically.
Therapy approaches for uncontrolled cell growth:
Cytostatics: These act almost exclusively on proliferating cells. They therefore have a particularly good effect on cells with a high growth factor and a short doubling phase (e.g. tumour cells in acute lymphatic leukaemia of the child, with good chances of cure).
Phase-specific cytostatics: these only work in certain cell cycle phases. Antimetabolites in the S phase; mitosis inhibitors in the M phase.
Non-phase-specific cytostatics: these act in all phases of the cell cycle. Most alkylating cytostatic drugs belong to this group.
Combination of cytostatic drugs: By combining several cytostatic drugs, their effect can be increased. The cells are attacked in different phases of the cycle. Developments in resistance can be reduced.
Targeted tumour therapeutics: The targets of these therapeutics are biologic features of the tumour cells, such as the overexpression of membrane-bound receptors (e.g. HER-2 in breast cancer). Their effect is independent of the cell cycle.
Resistance to tumour therapeutics: It usually develops through mutation and the subsequent therapy-related selection of tumour cells with survival advantage. There are different mechanisms for the development of resistance:
- Reduced uptake of the therapeutic agent into the cell (e.g. by reduced expression of the folate transporter in methotrexate)
- Increased DNA repair of cytostatic-induced damage
- Overexpression of target proteins for cytostatic drugs: e.g. dihydrofolate reductase in methotrexate
- Increased inactivation of the cytostatic drug
- Inhibition of apoptosis by overexpression of anti-apoptotic proteins
- Massively increased outward transport of the cytostatic drug out of the cell through overexpression of ABC transporters (e.g. P-glycoprotein transports anthracyclines out of the cell).
Undesirable effectsThis section has been translated automatically.
Although nowadays complex concomitant treatments are used to accompany cytostatic drugs, some therapies still have to be reduced in dose, interrupted or even discontinued. The WHO classification of side effects into degrees of severity depends on the measures taken in each individual case:
- Grade 0: no side effects
- Grade 1: Low side effects
- Grade 2: General condition worsens, chemotherapeutic drugs must be reduced
- Grade 3: Interruption of chemotherapy necessary
- Grade 4: Inpatient hospital treatment required
- Grade 5: Death by chemotherapy
The symptom complex of subjective fatigue of some patients treated with cytostatic drugs, which frequently occurs as a side effect, triggered by the above-mentioned changes in the blood count, is called fatigue.
LiteratureThis section has been translated automatically.
- Graefe KH et al. Malignant tumors, basics. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S. 655-682