Particle therapy and cancer treatment
Cancer cells are particularly vulnerable to DNA damage due to their high replication rate. Their poor DNA repair mechanisms also contribute; cancers themselves arise from faulty, unrepaired DNA so they do not have effective ways of fixing damage. Hence, radiotherapy can effectively reduce tumour size. However, this does not mean that healthy cells near the tumour are safe from radiation. DNA damage can also lead to cell death in healthy tissues, with fast-replicating, labile cells such as blood cells and stem cells particularly at risk. Harm to cells far from the tumour has also been observed; this is known as the radiation-induced bystander effect (RIBE). The mechanism for this is still not completely understood. The result of this damage is a plethora of side effects, such as fatigue, confusion, skin conditions, nausea, loss of appetite and fertility problems. 3 This places limits on the usefulness of X- ray and gamma radiotherapy, since, though a higher dose may be more effective against the cancer, it would also lead to increased damage to healthy tissues which could reduce life expectancy and quality of life. 4
New technologies seek to address this issue by using subatomic particles, instead of electromagnetic radiation, to target tumours. The most well-known and advanced of these modalities is proton therapy. Proton therapy involves firing a beam of positively-charged protons towards the site of the cancer. Like photons, protons are able to ionize atoms in DNA as well as causing the formation of ROS from surrounding molecules. The main mechanism for ionization of atoms using protons is through Coulombic interactions with electrons. Protons are positively-charged, while electrons are negatively-charged. This means that the
Figure 6: A collision between an incoming proton and a nucleus
passing protons attract electrons in the shells of nearby atoms. This attraction can pull electrons free from their atoms, creating ions. Though they experience a force of the same magnitude, the protons’ paths do not change significantly as their mass is about 1836 times greater than that of electrons, meaning they undergo a much smaller acceleration. A unique feature of proton therapy compared to conventional radiation therapy is the ability of protons to damage the tumour through nuclear reactions (Fig. 2). Collisions between protons and atomic nuclei can release a cascade of particles capable of damaging the DNA of cancer cells, such as more protons, alpha particles and neutrons, in addition to gamma radiation. This could enhance the effectiveness of the therapy.
However, without a doubt the greatest benefit of proton therapy is the increased precision with which the beam can target the tumour. Photons tend to deposit the greatest dose at the entrance of the tissue (Fig. 3), with the dose gradually decreasing with distance thereafter. This means that a comparatively dose is deposited at the site of the tumour, with significant entry and exit doses causing damage to healthy tissue. Unlike photons, protons have a very high linear energy transfer
Figure 3: Relative dose against distance for different radiotherapies
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