|Year : 2017 | Volume
| Issue : 3 | Page : 121-122
Chromatin landscape: Re-shaping radiation biology and oncology
Asmita Sharda, Sanjay Gupta
Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai; Homi Bhabha National Institute, Training School Complex, Mumbai, Maharashtra, India
|Date of Web Publication||17-Oct-2017|
Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai; Homi Bhabha National Institute, Training School Complex, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sharda A, Gupta S. Chromatin landscape: Re-shaping radiation biology and oncology. J Radiat Cancer Res 2017;8:121-2
On a dark November evening in 1895, German physicist W.C. Röntgen stumbled on radiation that could blacken photographic films, which he named as X-rays. Röntgen won various accolades, including the first Nobel Prize in Physics for his breakthrough. Sparked off by Röntgen's observations, the turn of the 19th century marks an important epoch in the history of radiation science. Just 2 years later, in 1903, Nobel Prize in Physics was awarded to Becquerel and Curie for the discovery of radioactivity. Soon medical prospects for X-rays began to be investigated. The emergence of the science of radiation oncology began as early as 1896, when X-rays were shown to treat hairy moles. Studies in radiation biology advanced rapidly, and even before the structure of DNA was discovered, H.J. Muller demonstrated that X-rays can cause mutations and was rewarded the Nobel Prize in Physiology in 1946.
Today, in the 21st century, radiation science is an indispensable part of health facilities, used in both routine diagnostic services and as an important treatment modality for even the deadliest of tumors. The prospects of radiation oncology have increased through technological advances such as IMRT, IGRT, SBRT, and newer forms of particle radiation. As reviewed in Boss et al., 2014, radiotherapy is able to tackle the hallmarks that a cancer cell displays. Yet, there are few challenges that radiobiology cannot overcome, owing to misregulated and transformed biological landscape of a cancer cell.
Radiobiology works on its 4 R's principle, namely, Repair, Reoxygenation, Repopulation, and Redistribution/Reassortment. Radiation targets major cellular pathways such as DNA repair, activity of which is influenced by DNA damage propagated by the presence of oxygen–oxygen effect, which in turn affects cell proliferation by influencing cell cycle redistribution. Yet, most radiation oncologists will acknowledge that another R, that is, radioresistance (intrinsic) has long been a pain for them since it is least understood what causes intrinsic radioresistance in tumors and nonresponding patients, thus leading to maximum relapse after radiotherapy.
It will not be an underestimation to comment that cell cycle phase is a major contributor toward success or failure of radiotherapy, the clear reasons for which are still elusive. Cell cycle phases vary in their sensitivity toward radiation, which is the basis of reassortment that results in sensitization of cancer cells in fractionated radiation. It had been demonstrated as early as the 1960s that radiosensitivity is maximum in mitotic cells and minimum in late S-phase of cell cycle. This may partially be attributed to the extent of DNA damage and repair., Since cell cycle is an important determinant for achieving success in radiotherapy, yet achieving complete synchrony in a tumor before treatment is a near impossible and ineffective goal, owing to kinetic variation because of tumor heterogeneity.
One way by which this limitation can be overcome is by understanding how chromatin architecture modulation takes place in each phase of the cell cycle after radiation-induced DNA damage. Chromatin landscape constantly changes as per the cellular requirement, external stimuli, and physiological states such as cancer. Thus, it may be interesting to understand how changes in chromatin can influence DNA repair response in each phase of the cell cycle. This may lead to a better understanding if there is actually any epigenetic basis to radio-resistance. Understanding of an epigenetic connection to radioresistance may be extremely useful for radiation therapy because by subsequently real-time estimation of chromatin modifying enzymes, it may be possible to mimic the epigenetic landscape of mitotic cells in interphase cells, thus potentially increasing their sensitivity toward radiation. This strategy may also be beneficial for cancer-stem cell-like cells and hypoxic populations, which are mostly quiescent (i.e., G0 phase), nonproliferative, refractory to treatment, and mainly responsible for relapse.
Although research is being carried out in the combined fields of radiation and epigenetic changes that follow, we need to adopt a unified approach that encompasses cell cycle and epigenetic changes in response to radiation to have maximum positive impact on both basic sciences and bench to bedside translational successes.
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