Cancer Biology
Ayesha Tungekar
RADIOTHERAPY FOR CANCER
Radiotherapy aims to eradicate cancer cells while minimally killing normal cells. Advancements in radiation treatment like image guide radiation therapy, stereotactic body therapy(SRT), and intensity-modulated radiation therapy have facilitated the delivery of the optimum matching doses to the exact tumor dimension, thereby minimizing the exposure of radiation to normal tissue. Cancer stem cells are the primary source of radiation. Resistance to radiation therapy can be due to tumor heterogenicity. Cancer is heterogeneous, and it involves metabolic, genetic, pathophysiological, and immune complexities. Over the last 20 years, the focus has been made to identify radiosensitizers and protectors which has widened the area of radiotherapy from ‘one size fits all to a more broad and dynamic treatment modality(Chen & Kuo, 2017)
Combined treatment in Colorectal cancer:
Histone Deacetylase targets histone deacetylase and thereby influences the chromatin structure. They can also regulate cellular function by acting on non-histone protein deacetylation and thus are involved in altered cancer cell pathways like apoptosis, DNA repair, and cell cycle. Valproic acid (VPA) is used for treating the anti-epileptic disorder. VPA has minor toxicity and a better safety profile than HDACis. In colorectal cancer cells (CRC) the p53 activity is dysregulated and the loss of function of p53 results in resistance to cancer therapies. In the experiment, four-cell models were used HCT116p53, p53 null subline HCT-116 p53 -/-, HT29and SW260 mutant cell lines. Transcription synthase (TS) upregulates thymidine phosphorylase (TP). TP is responsible for converting capecitabine to 5-Fluorouracil. Overexpression of TS is associated with less chance of survival in patients having a tumor and showing resistance to 5-FU. A combination of HDACi valproic acid and fluoropyrimidine-based radiotherapy on colorectal cancer cells was assessed. This combination treatment of VPA -5’DFUR and radiotherapy increased p53 phosphorylation at serine 37 despite being mutated and regulated cell growth and death. Combined treatment showed a synergistic effect on wild and mutant CRC cells, whereas a Synergistic effect was observed in HCT-116 p53 -/- cells. The results thus showed anti-proliferative, pro-apoptotic effects in p53 expressing cells when given a combined treatment of VPA fluoropyrimidine and radiotherapy. (Terranova- Barberio et al., 2017)
Cancer Biology – Ayesha Tungekar
Radiation therapy in breast cancer treatment:
Radiation therapy is effective in the treatment of breast cancer. PMRT(Postmastectomy radiation therapy) is effective for the treatment of supra-infraclavicular lymph nodes, treatment of internal mammary nodes, and treatment of chest wall; however, during the treatment of intramammary nodes, it damages lung and heart and leads to non-breast cancer mortality. The researchers divided the data into two groups and observed that patients which were treated with outdated RT had damaging effects on their hearts. In contrast, patients who received newer treatments had comparatively fewer side effects on the heart. (Haussmann et al., 2020)
Partial breast irradiation(PBI) is an attractive alternative method to reduce exposure of other organs to any side effects. It provides the best results in a shorter period. PBI is not suitable for treating a certain group of patients with a higher biological reoccurrence rate. (Haussmann et al., 2020).
Radiopharmaceutical therapy(RRT) involves administering radioactive atoms systemically to tumour-associated target sites, similar to chemotherapy. Beta particle emitting RPT is used for treating neuroendocrine cancer.
Hypoxia is a distinctive feature of solid tumors. It is associated with genomic instability and metastasis. Hypoxic radiosensitizers like Nimorazole is used to treat radiation-induced damage under hypoxic condition. A combination of imidazole along with radiation showed improvement in the control of HNSCC by 80 %. (Chen & Kuo, 2017)
Radiation can activate various host-immune responses, thereby improving the efficacy of radiotherapy. Radiation causes the release of tumor antigens. These tumor antigens are further captured and processed by antigen-presenting cells(APCs) into small peptides. These peptides are displayed on the surface of APC via MHC class I. The cytotoxic T cells (CTLs)interact with the MHC class I displaying the antigenic peptides, and thus cytotoxic CD8 T cells get activated. Activated CTLs are recruited toward tumor cells to attack them and generate the abscopal effect. Radiation causes an increase in cell surface receptor Fas on tumor cells. Fas interact with Fas-L. This caused an increase in T cell-mediated cytotoxicity and release of cytokines and DAMP, which elicit the primary and metastatic tumor cell killing. (Chen & Kuo, 2017)
PDT(photodynamic therapy) on combining with RDT can reduce the toxicity arising during the treatment
And also simultaneously eliminate tumors. Nanoparticles are being used for the effective combination of PDT with RT(radiotherapy) to eliminate. Xray is used to stimulate nanoparticles, the stimulated nanoparticles emit luminescence and are used for PDT activation. The radiation dose that needs to be given in vivo to illuminate the PDT is yet to be found out. Also, the exact time interval between the administration PDT and RDT needs to be determined. The toxicity arising from this combinatorial treatment is also yet to be identified. (Xu et al., 2016)
REFERENCE
Chen, H., & Kuo, M. T. (2017). Improving radiotherapy in cancer treatment: Promises and challenges. Oncotarget, 8(37), 62742–62758. https://doi.org/10.18632/oncotarget.18409
Haussmann, J., Corradini, S., Nestle-Kraemling, C. et al. Recent advances in radiotherapy of breast cancer. Radiat Oncol 15, 71 (2020). https://doi.org/10.1186/s13014-020-01501-x
Terranova-Barberio, M., Pecori, B., Roca, M.S. et al. Synergistic antitumor interaction between valproic acid, capecitabine and radiotherapy in colorectal cancer: critical role of p53. J Exp Clin Cancer Res 36, 177 (2017). https://doi.org/10.1186/s13046-017-0647-5
Xu, J., Gao, J., & Wei, Q. (2016). Combination of Photodynamic Therapy with Radiotherapy for Cancer Treatment. Journal of Nanomaterials, 2016, 8507924. https://doi.org/10.1155/2016/8507924
Research Writer
Ayesha Tungekar