Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells

Bhatt, Anant Narayan; Chauhan, Ankit; Khanna, Suchit; Rai, Yogesh; Singh, Saurabh; Soni, Ravi; Kalra, Namita; Dwarakanath, Bilikere S.

doi:10.1186/s12885-015-1368-9

Cited by 92 publications

(88 citation statements)

References 37 publications

(50 reference statements)

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“…Enhanced aerobic glycolysis is one of the prominent phenotypes of a majority of cancer cells which facilitate proliferation and confer protection against death, besides energy production [122,123]. This induced glycolysis is one of the major factors that contribute to IL-6-induced therapeutic resistance in cancer.…”

Section: Metabolic Remodellingmentioning

confidence: 99%

Role of interleukin-6 in cancer progression and therapeutic resistance

et al. 2016

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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.

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Section: Metabolic Remodellingmentioning

confidence: 99%

Role of interleukin-6 in cancer progression and therapeutic resistance

et al. 2016

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“…They also demonstrated that the radioresistance of cells induced by DNP was obtained by reducing residual DNA damage and cytogenetic damage linked to mitotic death via the non-homologous end joining and homologous recombination pathways [16]. Tumor hypoxia is a common phenomenon revealed to be an important effector promoting tumor cell survival.…”

Section: The Warburg Effect and Radioresistancementioning

confidence: 99%

Warburg effect, hexokinase-II, and radioresistance of laryngeal carcinoma

Zhong

Zhou

2016

Oncotarget

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Radiotherapy is now widely used as a part of multidisciplinary treatment approaches for advanced laryngeal carcinoma and preservation of laryngeal function. However, the mechanism of the radioresistance is still unclear. Some studies have revealed that the Warburg effect promotes the radioresistance of various malignant tumors, including laryngeal carcinoma. Among the regulators involved in the Warburg effect, hexokinase-II (HK-II) is a crucial glycolytic enzyme that catalyzes the first essential step of glucose metabolism. HK-II is reportedly highly expressed in some human solid carcinomas by many studies. But for laryngeal carcinoma, there is only one. Till now, no studies have directly targeted inhibited HK-II and enhanced the radiosensitivity of laryngeal carcinoma. Accumulating evidence has shown that dysregulated signaling pathways often result in HK-II overexpression. Here, we summarize recent advances in understanding the association among the Warburg effect, HK-II, and the radioresistance of laryngeal carcinoma. We speculate on the feasibility of enhancing radiosensitivity by targeted inhibiting HK-II signaling pathways in laryngeal carcinoma, which may provide a novel anticancer therapy.

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“…This feature of cancer cells, termed "the Warburg effect," has been considered to provide tumor cells selective advantages since the increased uptake of nutrition will provide sufficient raw materials for the synthesis of building blocks to satiate rapidly dividing cancer cells. Recently, studies focused on "the Warburg effect" revealed that elevated glycolysis of cancer cells will not only provide a growth advantage but also involves in resistance to chemotherapy and ionizing radiation resistance [10,11]. Therefore, inhibition of glycolytic metabolism during or after radiotherapy may be potentially exploited for identifying new drug targets for overcoming radioresistance.…”

Section: Introductionmentioning

confidence: 99%