Cancer is the disease before which humanity feels the most helpless. Every year, the number of cancer patients continues to rise at an alarming rate. It is estimated that one in every five people worldwide will develop cancer at some point in their lifetime.
All countries maintain detailed statistics on cancer patients. Yet, in many parts of the world, a large number of people die from cancer before the disease is even diagnosed. These deaths are not included in official statistics. According to the latest data from the International Agency for Research on Cancer (IARC), nearly 20 million new cancer cases were diagnosed globally in 2022 alone. In that single year, more than 9.7 million people died from cancer [1].
Due to major advances in science, technology, and medicine, human life expectancy has increased significantly. This has had a direct impact on the number of cancer patients. As people live longer, the likelihood of developing cancer in old age also increases. As a result, the number of cancer patients is rising sharply every year.
Based on an analysis of current statistics, scientists estimate that by 2030, the annual number of new cancer cases worldwide will rise to approximately 24 million, while about 12 million people will die from cancer each year. By 2040, this rate will increase further, with nearly 30 million new cases annually and more than 15 million deaths. By 2050, the situation will worsen even more: around 35 million new cancer cases will be diagnosed each year, and the mortality rate will exceed 50 percent. This means that one out of every two cancer patients will die. These figures are nothing short of a slap in the face for modern medical science.
There was a time when cancer was considered a disease of the wealthy. Statistics from the last century support this notion. For example, the percentage of cancer patients in Australia was much higher than in poorer African countries. One major reason was that average life expectancy in Africa was much lower than in Australia. Many people in Africa died from other treatable diseases long before reaching the average age at which cancer typically develops. But the world has changed significantly. The benefits of global development have reached even the most remote corners of the planet. In most countries, life expectancy has increased. Cancer is no longer a disease of the rich alone.
However, a serious problem remains. Because conventional cancer treatments are highly technology-dependent and extremely expensive, cancer care has not yet become universally accessible. As a result, mortality rates among cancer patients in wealthy countries are much lower than those in poorer nations.
In Bangladesh, 167,000 new cancer cases were diagnosed in 2022, and in the same year, nearly 117,000 people died from cancer. There are numerous obstacles to cancer diagnosis in Bangladesh. The healthcare system is fragile for various reasons. Many patients die from cancer before it is diagnosed, or it is detected only at a very late stage. Consequently, the annual cancer mortality rate in Bangladesh exceeds 70 percent.
This does not mean that cancer is untreatable. There are various treatments available, and a significant number of patients do recover. However, the main challenge is that the primary cause of cancer remains unknown. Because of this, medical science has not yet been able to identify a definitive method for cancer prevention. Since the root cause is unknown, cancer evokes intense fear among people and gives rise to numerous theories and claims—most of which remain unresolved.
Even though the root cause of cancer has not been identified, one fact is certain: cancer is not an infectious disease. Cancer is a cellular disease. Normal cells within the body transform into cancer cells. Scientists understand the process of this transformation, but they cannot predict when a normal cell will become cancerous. Although the transformation of cancer cells can be described scientifically, why it occurs remains unknown.
A cell’s functions are encoded in its DNA. There are clear differences between the DNA of normal cells and that of cancer cells. Abnormal changes in DNA disrupt normal cellular behavior, turning healthy cells into cancer cells. Cancer cells no longer obey the body’s natural biological instructions. A normal cell divides a fixed number of times and then undergoes natural death. Cancer cells do not follow this programmed death process. Therefore, killing cancer cells by any means necessary forms the foundation of cancer treatment.
Among conventional cancer treatments, one of the most important methods is the use of ionizing radiation to destroy cancer cells. Different treatment techniques have been developed based on how radiation is delivered to tumors containing cancer cells.
Most cancer patients receive chemotherapy, in which chemical radioactive substances are introduced into the body and directed toward cancer cells. If a tumor can be removed surgically, surgery is performed. Nearly half of all patients receive radiation from outside the body—a treatment known as radiotherapy. Radiotherapy has long been a reliable method of cancer treatment.
Eliminating cancer by destroying cancer cells is difficult because cancer cells are intermingled with normal cells. It is not possible to destroy all cancer cells at once, as doing so would also damage the surrounding healthy cells. If too many normal cells are destroyed, the body’s normal functions are disrupted, harming the patient rather than helping them. Therefore, in conventional radiotherapy, radiation is carefully administered so that cancer cells are destroyed while the functions of normal cells are preserved [2].
To protect normal cells from the harmful effects of radiation, conventional radiotherapy exploits certain biological differences between cancer cells and normal cells. For example, normal cells can automatically repair damaged DNA if they are given sufficient time. Therefore, instead of delivering a high dose of radiation all at once, conventional radiotherapy administers small doses at regular intervals. The interval between two radiation sessions (usually about 24 hours) allows the normal cells damaged by radiation to repair themselves through DNA repair mechanisms. Cancer cells generally lack this ability.
Cancer cells typically have lower oxygen supply than normal cells. When oxygen levels are low, the effectiveness of radiation decreases. As a result, destroying hypoxic (low-oxygen) cancer cells requires higher radiation doses, but such doses would severely damage surrounding normal cells. To avoid this, radiation doses must be kept lower, which leads to longer treatment durations, increased costs, and greater patient suffering.
Efforts to improve radiotherapy have been ongoing for decades. While incremental improvements have been achieved, no truly revolutionary breakthrough has occurred. Recently, however, scientists have begun to see the potential for extraordinary benefits in cancer treatment through a new approach known as FLASH radiotherapy, which delivers ultra-high-dose radiation [3,4].
FLASH radiotherapy is a technology that delivers an extremely high dose of radiation (greater than 40 Gy per second) to the body within an ultra-short time frame (milliseconds). In conventional radiotherapy, delivering just a few grays of radiation takes several minutes, whereas FLASH radiotherapy delivers the prescribed dose in less than one second. Remarkably, this rapid, ultra-high-dose radiation appears to destroy cancer cells effectively while causing significantly less damage to normal cells. This raises a critical question: How is this possible? If normal cells are damaged even at low radiation doses, how can they tolerate ultra-high doses?
Studies conducted on mice and pigs have shown that FLASH radiotherapy can effectively destroy cancer cells while sparing normal tissue. In 2019, FLASH radiotherapy was experimentally applied to a human patient for the first time in Switzerland. Currently, clinical trials are underway in the United States, France, and several European countries to evaluate its effectiveness. Scientists are testing various hypotheses to determine why normal cells survive FLASH radiotherapy.
The most widely accepted explanation for the survival of normal cells under ultra-high-dose radiation delivered in an extremely short time is the oxygen depletion hypothesis.
In conventional low-dose radiotherapy, radiation induces chemical reactions within biological cells that produce free radicals. In the presence of oxygen, these free radicals are converted into harmful peroxides, which damage DNA. Oxygen makes DNA damage permanent, preventing cells from repairing it through normal biological processes. However, if oxygen levels are low or absent, these free radicals cannot cause permanent DNA damage. As a result, even if DNA is temporarily damaged, cells can repair it naturally.
In FLASH radiotherapy, a very high dose of radiation is delivered within milliseconds. This produces an enormous number of free radicals that rapidly consume surrounding oxygen. Oxygen is depleted so quickly that cells experience temporary hypoxia. As a result, fewer peroxides are formed in normal cells, leading to less permanent DNA damage. Tumor cells, however, are often already hypoxic, so the oxygen-depletion effect of FLASH radiotherapy does not significantly protect them.
This hypothesis has been supported by experiments conducted on mice and other animals, suggesting the potential for a new revolution in cancer treatment. However, the path forward remains long. Different cell types absorb oxygen in different ways and at different rates. Moreover, radiation interacts differently with human cells than with animal cells, and radiation sensitivity varies across tissues. Therefore, the oxygen depletion hypothesis is not yet conclusively proven.
Even if this hypothesis is validated, significant challenges remain before FLASH radiotherapy can be widely applied in clinical practice. Technologies capable of delivering radiation at such ultra-high dose rates do not yet exist. The linear accelerators used in conventional radiotherapy cannot produce FLASH radiation. Another major challenge is the absence of reliable dosimeters capable of accurately measuring such high dose rates. Without precise dosimetry, it is impossible to deliver controlled radiation doses to patients. From a technological standpoint, FLASH radiotherapy is expected to be far more expensive than conventional radiotherapy, raising concerns that cancer treatment could once again become accessible only to the wealthy.
Despite these limitations, FLASH radiotherapy holds the potential to revolutionize future cancer treatment, particularly for cancers located in radiation-sensitive organs such as the brain and lungs. If ongoing research is successful, it could enable faster treatments, fewer side effects, and more effective outcomes.
References
1. Global Cancer Observatory, Cancer Today, 2024.
2. Pradip Deb, Physics in Diagnosis and Therapy, Prothoma, Dhaka, 2023.
3. Frontiers in Oncology, Volume 9, Article 1563, January 2020.
4. Oncology Letters, Volume 28, Article 602, 2024.
