Role of interleukin-6 in cancer progression and therapeutic resistance.
In the last several decades, the number of people dying from cancer-related deaths has not reduced significantly despite phenomenal advances in the technologies related to diagnosis and therapeutic modalities. The principal cause behind limitations in the curability of this disease is the reducing sensitivity of the cancer cells towards conventional anticancer therapeutic modalities, particularly in advance stages of the disease. Amongst several reasons, certain secretory factors released by the tumour cells into the microenvironment have been found to confer resistance towards chemo- and radiotherapy, besides promoting growth. Interleukin-6 (IL-6), one of the major cytokines in the tumour microenvironment, is an important factor which is found at high concentrations and known to be deregulated in cancer. Its overexpression has been reported in almost all types of tumours. The strong association between inflammation and cancer is reflected by the high IL-6 levels in the tumour microenvironment, where it promotes tumorigenesis by regulating all hallmarks of cancer and multiple signalling pathways, including apoptosis, survival, proliferation, angiogenesis, invasiveness and metastasis, and, most importantly, the metabolism. Moreover, IL-6 protects the cancer cells from therapy-induced DNA damage, oxidative stress and apoptosis by facilitating the repair and induction of countersignalling (antioxidant and anti-apoptotic/pro-survival) pathways. Therefore, blocking IL-6 or inhibiting its associated signalling independently or in combination with conventional anticancer therapies could be a potential therapeutic strategy for the treatment of cancers with IL-6-dominated signalling.
Division of Metabolic Cell Signalling Research, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Road, Delhi, 110 054, India.|Department of Biotechnology, Delhi Technological University, Delhi, 110042, India.
Neeraj
N
Kumari
Central Research Facility, Sri Ramachandra University, Chennai, 600116, India.
B S
BS
Dwarakanath
Department of Biotechnology, Delhi Technological University, Delhi, 110042, India.
Asmita
A
Das
Division of Metabolic Cell Signalling Research, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Road, Delhi, 110 054, India. anant@inmas.drdo.in.
Anant Narayan
AN
Bhatt
D004249:DNA Damage; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007249:Inflammation / Q000209:etiology; D015850:Interleukin-6 / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D010084:Oxidation-Reduction; D059016:Tumor Microenvironment; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human
Cancer; Chemotherapy; IL-6; Radio-resistance; STAT-3; Therapeutic resistance