Ionising radiotherapy is a well-established, effective cancer treatment modality, whose efficacy has improved with the application of newer technological modalities. However, patient outcomes are governed and potentially limited by aspects of tumour biology that are associated with radioresistance. Patients also still endure treatment-associated toxicities owed to the action of ionising radiation in normoxic tissue adjacent to the tumour mass. Tumour hypoxia is recognised as a key component of the tumour microenvironment and is well established as leading to therapy resistance and poor prognosis. In this review, we outline the current understanding of hypoxia-mediated radiotherapy resistance, before exploring targeting tumour hypoxia for radiotherapy sensitisation to improve treatment outcomes and increase the therapeutic window. This includes increasing oxygen availability in solid tumours, the use of hypoxia-activated prodrugs, targeting of hypoxia-regulated or associated signalling pathways, as well as the use of high-LET radiotherapy modalities. Ultimately, targeting hypoxic radiobiology combined with precise radiotherapy delivery modalities and modelling should be associated with improvement to patient outcomes.

Background and purpose: Radiotherapy is used for the treatment of malignant tumours, and may be used as the primary therapy. It is also common to combine radiotherapy with surgery, chemotherapy, hormone therapy or some combination of them. Even if the tumour is treated intensively, women diagnosed with breast cancer may develop a recurrence. Most recurrences may be in the form of distant metastases, development of multi-drug resistance phenotype or both together. This study demonstrated that some of the multi-drug resistant cancer cells may also become radioresistant.

Materials and Methods: Chemoresistance in paclitaxel (MCF-7/Pac), docetaxel (MCF-7/Doc), vincristine (MCF-7/Vinc), doxorubicin (MCF-7/Dox) and zoledronic acid (MCF-7/Zol) resistant MCF-7 cells were demonstrated by XTT assay. MDR1 gene expression was detected by real-time PCR in human MCF-7 breast cancer cells. Drug resistant and sensitive cells were exposed to γ-radiation and development of radioresistance was investigated.

Results: Results have indicated that paclitaxel, docetaxel, vincristine, doxorubicin and zoledronic acid–selected cells gained varying degrees of resistance to their selective drugs when compared with original MCF-7/S. MCF-7/Pac, MCF-7/Doc, MCF-7/Vinc and MCF-7/Dox cells have all acquired MDR1 expression. Among the resistant sub-lines, MCF-7/Pac and MCF-7/Doc cells were significantly cross-resistant to irradiation compared to the sensitive cells.

Conclusion: MCF-7/Pac and MCF-7/Doc cell lines were found radioresistant to γ-radiation. On the contrary, doxorubicin, vincristine and zoledronic acid resistant cancer cells were still sensitive to radiation.

Eggs (1, 2 and 3-day-old), larvae (early and late) and 4-day-old pupae of the rice moth, Corcyra cephalonica (Stainton), were treated with 60Co gamma-radiation at doses from 0 to 100 krads. Evaluation of moth radiosensitivity by the survival of treated eggs, larvae and pupae led to the following sequence of stages in order of increasing radioresistance: for the eggs, 1, 2 and 3-day-old; for larvae and pupae, early larvae (5 days after hatching), late larvae (5 days before pupation) and 4-day-old pupae. Twenty five kiloradians was found to be the most likely unit for disinfestation by radiation of C. cephalonica.