To move forward on innovative treatments, we now need to understand the mechanism of action of conventional treatments such a chemotherapy and radiotherapy.
Cytotoxic chemotherapy is effective in the treatment of Hodgkin's disease (cancer of the lymph nodes) or cancer of the testis and the tumors of the children.
These anticancer drugs are extremely reactive. They cannot be injected into the thin peripheral veins, but must be infused slowly into reservoirs implanted under the skin and connected to the deep veins. From there, infusion of chemotherapy into the large central veins allows diluting these highly toxic molecules in a large flow of blood. Chemotherapy will reach the DNA of the tumor cell and inactivate it by breaking it into pieces. The DNA will be irreparable and the cell will die. This is what is written in the textbooks.
Govindan, R., DeVita, V. T. (Eds.). (2009). DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology Review. Lippincott Williams & Wilkins.
In fact, these molecules do not target only DNA, but also react with every cellular component and in particular proteins. If chemotherapy did simply kill the cells, the doctor should promptly measure the impact.
There is no detectable residue of these tumor cells which died, because of the injection of the chemotherapy, in the blood or in the urine of the patient. The oncologist is not capable of assessing within minutes or hours the efficacy of his chemotherapy. He has no way of knowing if he is injecting the right treatment.
It is usually easy to detect residues of dead cells in the blood, just as, following a heart attack, the cardiologist finds specific enzymes, such as troponin, normally present exclusively in the heart cells or in the blood. If the blood level of troponin is increased, heart cells have died and released troponin in the blood stream. The physician knows that he is dealing with a cardiac infarct.
During treatment of cancer by chemotherapy, the oncologist does not find any traces of cell death. He/she has to wait for weeks to assess the efficacy of treatment.
During treatment of cancer by chemotherapy, when the oncologist does not find any traces of cell death, a waiting period of weeks is needed to assess the efficacy of treatment.
The world of quantum physics is strange. The particles can be simultaneously in different places. Time and space no longer exist. Particles spin (turn on themselves) around an axis that could only point in a few directions in an external magnetic field. Electrons, protons and neutrons (particles of spin one-half) have thus only two directions of spinning, in one direction or in the opposite direction. A crucial point is that the chemical reactivity of atoms is radically different depending on the overall spin of the outer electrons.
Spin explains why oxygen gas exists in two very different states: singlet dioxygen and triplet dioxygen. The most stable form is triplet oxygen that is rather inert. This is in deep contrast with singlet oxygen that is highly reactive with a very short lifetime in a condensed medium.
We are writing this text on a wooden table. It bathes in the atmosphere rich in triplet dioxygen and yet it does not burn. In order for the wood to burn, oxygen must not be in its triplet form but in its singlet form. The firing of the match heats oxygen and change its quantum structure so that from triplet it becomes singlet oxygen. Singlet oxygen and the carbon of the wood will react to form carbon dioxide, releasing a large amount of entropy in the form of heat.
Singlet and triplet dioxygen have the same physical formula written as [O2]. The only difference is the spin of the electron. In the singlet form [1O2], there is pairing of the two electrons of the highest energy. One electron spin around a direction, while the second one spin in the opposite direction. By contrast, in triplet state [3O2], both electrons spin in the same direction. The singlet form of dioxygen is higher in energy and much more reactive than the triplet form. Various methods for the production of singlet oxygen exist. We can light a match or create a sparkle to change triplet into singlet dioxygen. In the laboratory, irradiation of oxygen gas by infrared in the presence of an organic dye as a sensitizer, such as Rose Bengal, Methylene Blue, or porphyrin results in its production.
When in excess, singlet oxygen will react with water to form ozone or O3 and hydrogen peroxide (H2O2). Ozone is a mighty oxidant. Exposure to ozone results in the oxidation and the destruction of the molecules of life such as DNA or the proteins to form carbon dioxide and nitrogen gas. For this reason, burning organic matter with ozone is clean and leaves no residues. This could explain the absence of corpses when ozone kills cells. They have been completely burnt into volatile gas and minerals.
Radiation therapy is together with surgery the most effective treatment for early stage cancer. When the tumor has not spread and is localized to its tumor bed, the treatment of choice is often a combination of limited surgery and irradiation of surrounding tissue.
Today, treatment of most early stage breast cancers involves limited surgery followed by radiation therapy to the entire breast and draining lymph nodes. The surgery allows removal of the bulk of the cancer, while radiation kills the few remaining cells.
The radiotherapist uses several beams of photons that converge on the diseased breast. The radiationtherapist disperse the dose to the healthy lungs ( to be below the threshold of toxicity) to focus radiation on the diseased breast. To sterilize cancer without causing insurmountable side effects, the radiotherapist has two tools at his disposal, the energy of the beam and the dose that he can deliver to the patient.
Modern linear accelerators deliver beams of over one million electron volts (1 MeV) penetrating into the patient to target deep-seated lesions. Textbooks teach us that the effect of X-rays has the consequence of DNA damage. Like cytotoxic chemotherapy, X-rays will cause DNA breaks, which will lead to irremediable damage and cell death.
Since the 1930s, radiotherapists have known that tumors where the oxygen supply is important are more sensitive to radiotherapy.
The oxygen effect has particular importance in external beam radiation therapy. Here, the killing of tumor cells with radiation therapy in well oxygenated regions can be up to three times greater than in a poorly vascularized portion of the tumor. It is why radiation is more effective in treating the well-oxygenated periphery of the cancer than the anoxic center. Such sensitivity to oxygen is not specific to cancer cells. Normal cells are also more sensitive to radiation in the presence of oxygen. As of today, the reason of this oxygen effect remains unknown.
In the laboratory, X-rays kill cells. In the patient, there is no sign of cell death after radiation therapy. The corpses of cells have disappeared !
Phototherapy uses much less penetrating rays : visible photons or even infrared. In one centimeter over 90% of the dose has been absorbed. To treat deep-seated lesions, the physicians have to insert a light source into the patient close to the tumor.
To treat a bladder cancer, the physician prescribes a molecule, such as Methylene Blue, which is activated by the light. Insertion of a catheter into the bladder will guide the light toward the tumor. Methylene Blue reacts with light photons and produces singlet oxygen. This singlet oxygen will react with the cancer and hopefully cure it.
Khan, A. U., Kasha, M. (1979). Direct spectroscopic observation of singlet oxygen emission at 1268 nm excited by sensitizing dyes of biological interest in liquid solution. Proceedings of the National Academy of Sciences, 76(12), 6047-6049.
Like linear accelerators used for radiation therapy, stars emit high-energy X-rays. Astronomers are thus specialists of the interaction of X-rays with water, the most abundant molecule in the universe. They note the synthesis of large amounts of a short-lived molecule such as singlet oxygen. Singlet oxygen will in turn damage proteins and DNA but above all synthesize ozone, presented earlier.
If the concentration of singlet oxygen is high enough, the quantity of ozone will be sufficient to destroy DNA, protein and membranes. There will be no cell corpse left. Several weeks later, the oncologist will palpate an increasingly soft tumor, which may melt away. Singlet oxygen has another effect. It will allow the mitochondria to breathe. The tumor will excrete its entropy in the form of heat and stop growing. But the efficacy of treatment does not lead to healing. At some point the cancer will start to grow again.