title: Sunitinib-induced asthenia: from molecular basis to clinical relief.
abstract: Asthenia-fatigue syndrome (AFS) is defined as a persistent, subjective sense of tiredness related to cancer or its treatment and greatly impacts quality of life among cancer patients. All tyrosine kinase inhibitors, but especially sunitinib, may induce AFS. The reason for sunitinib-induced AFS is not yet well understood. Adverse events caused by sunitinib associated with AFS may include anemia, hypothyroidism, nausea and vomiting. However, AFS is also reported when active treatment with sunitinib is ongoing, and no other relevant adverse event can justify it. The molecular mechanisms by which sunitinib triggers AFS remain elusive. Sunitinib displays multiple off-target tyrosine-kinase interactions and competitively inhibits multiple proteins through the blockade of their ATP-binding sites. The broad spectrum of kinases inhibited may play a key role not only in terms of activity but also in terms of toxicity induced by sunitinib. This study considered different clinical observations and current metabolic and pharmacological knowledge, leading to hypotheses regarding which molecular mechanisms may be involved in sunitinib-induced AFS in cancer patients. Deeper knowledge of the molecular mode of action of sunitinib may lead to improved optimization of its clinical use.
authors: Clinical Oncology Department, A Coruña University Hospital, A Coruña, Spain. Luis.M.Anton.Aparicio@sergas.es
authors: Luis M Antón
authors: LM
authors: Aparicio
authors: Enrique Grande
authors: EG
authors: Pulido
authors: Guadalupe Aparicio
authors: GA
authors: Gallego
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001247:Asthenia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015994:Incidence; D007211:Indoles / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D011758:Pyrroles / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib