Biological therapies

In recent years, the research for new antineoplastic drugs has led to the discovery of the so-called “biological” or “molecular target” or “intelligent” drugs.

Unlike traditional chemotherapics that simply attack cells that replicate very quickly, biological therapies only act on cancer cells that have specific targets. For this reason, they are much more targeted therapies that act directly on the tumor, saving normal cells with consequent less toxicity. They are personalized therapies based on the characteristics of the tumor.

The targets of these drugs are specific molecules that are altered in cancer cells and therefore responsible for the growth and uncontrolled spread of cancer cells (growth factors, receptors, enzymes, angiogenetic factors …).

The main limitation of these therapies is that they are limited to only some tumors because not all tumors express these altered molecules (drug targets). Furthermore, in many cases, although the biological therapy is very precise, it is not sufficient to block the development of the neoplasm; for this reason it is often necessary to associate it with chemotherapy.

To check if the patient can be subjected to such therapies, it is necessary to check that the tumor has the target molecular alteration of the therapy itself. For the identification of these alterations it is necessary to carry out investigations on the histological material taken during the biopsy.

The main classes of biological drugs are:

1. Monoclonal antibodies: they act by binding to molecules (antigens) present exclusively in cancer cells, blocking their activity.

The monoclonal antibodies currently on the market are:

      • Bevacizumab (avastin®) used in the treatment of:
        • Metastatic colorectal cancer
        • Metastatic breast cancer
        • Non-small cell lung cancer
        • Metastatic renal cell carcinoma
        • Ovarian cancer
        • Carcinoma of the uterine cervix
        • Peritoneal carcinoma
      • Rituximab (mabthera®) used in the treatment of:
      • Non-Hodgkin lymphoma
      • Lymphocytic leukemia
      • Cetuximab (erbitux®) used in the treatment of:
      • Colon cancer in the absence of a RAS mutation
      • Tumors of the head and neck
      • Trastuzumab (herceptin®) used in the treatment of:
      • HER-2 positive breast cancer
      • HER-2 positive carcinoma of the stomach
      • Pertuzumab (parjeta®) used in the treatment of:
      • HER-2 positive breast cancer
      • Alemtuzumab (lemtrada®) used in the treatment of:
      • Lymphocytic leukemia
      • Panitumumab (vectibix®) used in the treatment of:
      • Metastatic colorectal cancer
      • Ofatumumab (arzerra®) used in the treatment of:
      • Chronic lymphatic leukemia
      • Denosumab (prolia®) used in the treatment of:
      • Prostate cancer
      • Ramucirumab (cyramza®) used in the treatment of:
      • Non-small cell lung cancer
      • Gastric carcinoma
      • Adenocarcinoma of the gastro-esophageal junction
      • Colorectal cancer
      • Hepatocellular carcinoma

 

2. Tyrosine kinase inhibitors: they act by inhibiting the enzymatic activity of the mutated forms of proteins involved in tumor development or progression.

The tyrosine kinase inhibitors currently on the market are:

      • Erlotinib (tarceva®) used in the case of:
      • Non-small cell lung cancer with mutated EGFR
      • Pancreatic carcinoma
      • Gefitinib (iressa®), Afatinib (giotrif®) used in the case of:
      • Non-small cell lung cancer with mutated EGFR
      • Crizotinib (xalkori®), Ceritinib (zykadia®), Alektinib (alecensa®) used in the case of:
      • Non-small cell lung cancer with mutated ALK
      • Imatinib (glivec®) used in the case of:
      • Chronic myeloid leukemia
      • Acute lymphoblastic leukemia
      • Bortezomib (velcade®) used in the case of:
      • Multiple myeloma
      • Lapatinib (tyverb®) used in the case of:
      • HER2 positive breast cancer
      • Sunitinib (sutent®) used in the case of:
      • Advanced kidney cancer
      • Neuroendocrine pancreatic tumor
      • GIST
      • Sorafenib (nexavar®) used in the case of:
      • Hepatocellular carcinoma
      • Advanced renal cell carcinoma
      • Thyroid carcinoma
      • Palbociclib (ibrance®) used in the case of:
      • Hormone-sensitive and HER-2 negative breast cancer
      • Everolimus (afinitor®) used in the case of:
      • Hormone-sensitive and HER-2 negative breast cancer
      • Neuroendocrine pancreatic tumor
      • Neuroendocrine pancreatic or pulmonary tumor
      • Advanced kidney cancer
      • Regorafeinb (stivarga®) used in the case of:
      • Metastatic colorectal cancer
      • GIST
      • Hepatocellular carcinoma
      • Vemurafenib (zelboraf®) used in the case of:
      • Melanoma with BRAF mutation
      • Dabrafenib (tafinlar®) used in the case of:
      • Melanoma with BRAF mutation
      • Non-small cell lung cancer with BRAF mutation
      • Pazopanib (votrient®) used in case of
      • Advanced kidney cancer
      • Soft tissue sarcoma

 

Biological drugs are much more tolerated by the patient as they have milder and less frequent side effects than chemotherapy. However, the disorders that can appear are as follows:

      • Nausea
      • Diarrhea
      • Asthenia
      • Itchy skin
      • Rashes
      • Conjunctivitis
      • Visual changes
      • Impaired kidney and liver function

 

They can be administered:

      • orally
      • intravenously
      • subcutaneously

 

These targeted therapies are very expensive therefore they are administered only to those patients who really can benefit from them.

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