Side effects of anti-cancer molecular-targeted therapies (not monoclonal antibodies).
OBJECTIVE
Major advances have been achieved in the field of biologically based therapies for cancer in the last few years, and some of the recently approved 'molecular-targeted therapies' are now being used in daily clinical practice. We aim to review some aspects of the toxicity and safety of small-molecule anti-cancer molecular-targeted therapies, with some insights into the physiopathology and predictive factors of toxicity, its correlation with response, and how to prevent and overcome it.


RESULTS
As a whole, small-molecule molecular-targeted therapies are well tolerated. Their toxic profile is favorable, but during the drug development process some severe (sometimes lethal) toxicities have been observed, such as interstitial lung disease in patients treated with drugs targeting the epidermal growth factor receptor. Pharmacogenomic studies can help us to identify those patients with well characterized polymorphisms, and to define the best-tolerated and most effective treatments.


CONCLUSIONS
Molecular-targeted therapies have a good toxicity profile in general; however, some patients are exquisitely sensitive to developing particular and severe toxicities related to these drugs.
de Castro
Gilberto
G
Clinical Oncology Service, Radiology Department, InRad, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil.
Awada
Ahmad
A
D000970:Antineoplastic Agents / Q000009:adverse effects*; D001897:Boronic Acids / Q000009:adverse effects; D000069286:Bortezomib; D015195:Drug Design; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D000077269:Lenalidomide; D009369:Neoplasms / Q000628:therapy*; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011719:Pyrazines / Q000009:adverse effects; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D001897:Boronic Acids; D007155:Immunologic Factors; D011480:Protease Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D051231:Farnesyltranstransferase; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D046988:Proteasome Endopeptidase Complex; D000077269:Lenalidomide