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Proteasome inhibitors

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Proteasome is a cellular body responsible for removing protein no longer needed by the cell, thus giving the name 'cell's trash processor'. If proteasome functionality is inhibited, protein which should be removed accumulates in the cell. This interferes with the cell’s functionality and can cause it to die. Interestingly, cancer cells are 1000 times more susceptible to proteasome inhibitors compared to healthy cells. Drugs that stop 'cell's trash processor' are called proteasome inhibitors. Although they only target one cellular body, they affect numerous vital cellular processes, preventing development of cancer cells, their division and spread into other parts of the body.

Treating with proteasome inhibitors results in various possible side effects:  transient thrombocytopenia (reduced numbers of platelets), anemia, neutropenia (reduced number of white blood cells), herpes zoster, and peripheral neuropathy with pains in limbs, disturbances in the sense of touch, sensation of tingling and pins and needles in hands and feet can also be present. Peripheral neuropathy is partially or completely resolved in patients after the treatment has stopped or the drug dosage reduced.

Immunomodulatory drugs

These drugs affect patient’s immune system. Resistance to foreign cancer plasma cells is more effectively built up. Immunomodulatory drugs also inhibit formation of blood vessels and therefore inhibit the supply of nutrients to the cancer cells from the blood stream. Myeloma cells excrete cytokines which promote formation of new blood vessels that in turn enable better survival rates.
The most important unwanted side effects which occur when taking immunomodulatory drugs are hematological, e.g. the reduction of the red and white blood cell and platelets count, drowsiness and skin eczema is also common. Thrombosis and pulmonary embolism may affect the patient due to the blood clots when using these drugs for the patient’s treatment. To prevent their formation the physician shall prescribe acetylsalicylic acid or LMWH.
Similarly to Proteasome inhibitors, peripheral neuropathy can occur, but rarely.

Monoclonal antibodies

Similarly to lymphoma treatments, monoclonal antibodies are available for the treatment of multiple myeloma if the health insurance covers the cost. Monoclonal antibodies are directed to a certain protein located on the surface of the myeloma cell (e.g. CD 38 antigen, SLAM F7). When monoclonal antibody is bound to the protein, it starts an array of intra and extracellular processes that directly destroy the cancer cell, or this is achieved by activating patient’s immune system. This treatment’s modus operandi completely differs from that proteasome inhibitors or immunomodulatory drugs treatments. This is why excellent results can be achieved on patients who have already tried these treatments and are unresponsive to those methods.
Monoclonal antibodies treatment is given in the form of infusions which take place according to a precise timetable. Treatment with monoclonal antibodies (e.g. anti-CD 38 monoclonal antibody) is generally well tolerated, however unwanted side effects may occure. Unwanted side effects include those relating to hematology, infections, fatigue and nausea. While receiving infusion, especially in the first round of treatment, an infusion reaction can occur – symptoms are very similar to a common cold (sore throat, chills, cough, running nose, respiratory problems). Infusion reactions are usually mild, but it is important to notify the physician or nurse about any observed unwanted side effects. Monoclonal antibodies can be combined with immunomodulatory drugs or proteasome inhibitors, as well as corticosteroids.

HDAC inhibitors

Treatments which use inhibitors of histone deacetylases (HDAC) are directed at the cancer cell's DNA. By inhibiting the enzyme critical for the division of cancer cells, reproduction is stopped which triggers their death. HDAC inhibitors are used together with proteasome inhibitors and corticosteroids.
Possible side effects are diarrhea, which could also be very severe, hematological and heart unwanted side effects, infections, fatigue, nausea and vomiting.
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