Cancer-drug induced insulin resistance: innocent bystander or unusual suspect.
Epidemiological and experimental evidence strongly suggests an association between type 2 diabetes mellitus and cancer. Insulin resistance, causing hyperinsulinaemia and eventually hyperglycaemia, appears to increase cancer incidence and disease progression. In addition, insulin resistance seems to reduce the efficacy of cancer therapy. Treatment with cancer therapeutics such as glucocorticoids, chemotherapy, hormonal therapies and targeted drugs can actually induce insulin resistance. The question arises whether cancer-therapy induced insulin resistance impairs anticancer treatment efficacy and disease outcome. Here, we review current literature regarding the incidence of cancer-therapy induced insulin resistance and describe the systemic and extra- and intracellular changes that occur in insulin signalling pathways and glucose metabolism. Subsequently, clinical and preclinical evidence for consequences of insulin resistance in terms of cancer progression and survival is presented. Finally, potential interventions including diabetes medication and limiting energy availability through diets and exercise are discussed.
Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: g.ariaans@umcg.nl.
G
G
Ariaans
Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: s.de.jong@umcg.nl.
S
S
de Jong
Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: j.a.gietema@umcg.nl.
J A
JA
Gietema
Department of Vascular Medicine, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: j.d.lefrandt@umcg.nl.
J D
JD
Lefrandt
Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: e.g.e.de.vries@umcg.nl.
E G E
EG
de Vries
Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: m.jalving@umcg.nl.
M
M
Jalving
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced*; D019468:Disease Management; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D000970:Antineoplastic Agents
Cancer; Cancer therapy; Diabetes; Fasting; Insulin resistance; Metformin