Impact of Radiation Resistance on Cancer

Sidharth Bommakanti
March 1, 2021

Submitted as coursework for PH241, Stanford University, Winter 2021


Fig. 1: How the MET gene aids cancer. (Source: S. Bommakanti, after Jeon and Lee. [5])

Cancer has been widely known as one of the most complex and deadly diseases affecting millions of people every year. Approximately 1.9 million new cases of cancer will be diagnosed and over 600 million people will die from the disease just in 2021. [1] In the past decade however, the death rate for cancer has declined significantly due to increased early detection and treatment from improved technology as well lifestyle changes such as smoking reduction. [1] Still, much work needs to be done to understand the underlying mechanisms behind many of the more complex cancers to identify more reliable treatments with decreased side effects. Currently, for most cancers and tumors, the traditional route of treatment includes a combination of chemotherapy and radiation. While chemotherapy tends to be a more broad reaching approach that kills both the cancer cells as well as healthy cells, radiation has the ability to be targeted to specific areas. This makes the therapeutic potential for targeted radiation therapy endless.

One of the hallmarks of cancer is that the cells are rapidly undergoing mitotic division and proliferating at an abnormal and unsustainable pace. [2] The cells come together to create the mass that is a tumor. While experimental evidence is scarce and potentially unattainable, one commonly accepted theory is that radiation is effective against these dividing cells by breaking the DNA within them and causing a cascade of attempted repair mechanisms that end up in apoptosis, or cell death. [2] Unfortunately, as the cancer cells continue to mutate, some may begin to gain a resistance to the radiation and start metastasizing again.

Resistance to Cancers

Scientists have been currently conducting research on identifying the mechanism by which cancer cells are developing resistance. One promising area that has shown some success is within the MET oncogene. MET is a growth factor receptor protein that is highly expressed in many cancers and is associated with metastasis. Two of the main proteins that regulate MET are ataxia telangiectasia mutated (ATM) and nuclear factor kappa B (NF-kB). [3] Researchers hypothesized that the MET gene may be associated with increased resistance to radiation therapy by increasing membrane permeability and cell motility while also increasing cell proliferation. This leads to an increase in angiogenesis which can help provide the nutrients for cancer cell survival as shown in Fig. 1. Experiments using mouse models showed that after radiation treatment, there were large increases in activation of NF-kB and ATM which led to a 5-fold increase in the expression of the MET gene. [3] The tumor cells that then survived became more robust and were able to proliferate at a faster pace. Using western blot and qPCR technology data, they also saw that individuals with statistically significant increases in levels of phosphorylated MET (pMET) and MET saw a 1.28 (OR=1.28) times increase in chances of death from their cancer. [3] Separate studies that worked to target the MET gene using small molecule kinase inhibitors saw statistically significant tumor shrinkages as well. [3] While more research needs to be done, it is essential to continue working towards finding a cure to cancer by identifying ways to enhance the therapeutic effect of radiation while decreasing resistance.


The field of cancer therapeutics is vast and constantly growing with researchers looking at many different avenues to find the best possible treatment with the least possible side effects. Due to the ability of radiation to target specific areas, it is an ideal area to focus on for the future. While the MET gene is a promising target for finding a reliable cure to cancer, it is just one possible option and scientists are continuing to look at a variety of avenues for treatment such as CAR-T cell therapy and targeted immunotherapies as well other genes such as the AKT gene. [4] Though we are far from a complete cure to cancer devoid of resistance, we are continuing taking steps in the right direction that may bring great insight in the coming years.

© Sidharth Bommakanti. The author warrants that the work is the author's own and that Stanford University provided no input other than typesetting and referencing guidelines. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.


[1] S. J. Henley et al., "Annual Report to the Nation on the Status of Cancer, Part I: National Cancer Statistics," Cancer 126, 2225 (2020).

[2] R. Baskar et al., "Biological Response of Cancer Cells to Radiation Treatment," Front. Mol. Biosci. 17, 24 (2104).

[3] F. De Bacco et al., "Induction of MET by Ionizing Radiation and Its Role in Radioresistance and Invasive Growth of Cancer," J. Natl. Cancer Inst. 103, 645 (2011).

[4] P. K. Todorova, B. Mukherjee, and S. Burma, "MET Signaling Promotes DNA Repair and Radiation Resistance in Glioblastoma Stem-Like Cells," Ann. Transl. Med. 5, 61 (2017).

[5] H.-M. Jeon and J. Lee, "MET: Roles in Epithelial-Mesenchymal Transition and Cancer Stemness," Ann. Transl. Med. 5, 5 (2017).