the Problem

According to the WCRF and WHO, colorectal cancer is the third most common cancer worldwide, the third most common in men and the second most common in women. Despite the enormous efforts dedicated to prevention and early detection, in 2020, more than 1.9 million of new cases were diagnosed, making colorectal cancer the second most common cause of death in cancer patients. These numbers indicate that the preventive and screening actions in place nowadays are largely insufficient. People with an apparent healthy way of life can still develop colorectal cancer, and even when the disease is detected at an early stage, it is not certain that it will be defeated without recurring again in the future. For these reasons, there is necessary to provide effective, innovative, and personalized methods to intercept the cancer drivers, instead of cancer itself only when present, so that we can also lower the huge social and economic burden the disease has on society. Nowadays, most people think that cancer prevention is a passive process that requires avoiding risk factors (e.g. tobacco smoke) to prevent the development of the disease (e.g. lung cancer). This is called “primary prevention” and is fundamental. However, in recent years, the importance of other approaches has emerged. In fact, just like cardiovascular disease (CVD) can be intercepted with drugs that reduce CVD risk (such as antihypertensive or cholesterol-reducing drugs), cancer development can be intercepted with risk-reducing agents too. The use of preventive agents that are active against lung cancer that develops in former smokers is a case in point of how new, active approaches can prevent cancer before the advanced stage of the disease is clinically detected. The idea of CVD interception has been widely accepted. The use of antihypertensive agents in high-risk patients with severe hypertension or with class III/IV heart failure, the use of statins in patients with prior myocardial infarction and very high low-density lipoprotein (LDL) cholesterol, and the use of aspirin in patients with prior MI or stroke are the first success stories in the field.

These strategies are now CVD prevention standards once considered effective therapies in advanced diseases. On the other hand, up to now the idea of cancer interception has been a hard sell, even among educated people prone to trying active prevention for their personal health. Troubles with adherence to risk reduction-based approaches (e.g. the use of effective breast cancer risk-reducing agents) are around the corner. One proposed hindrance is the risk of toxic effects, such as adverse cardiovascular effects produced by nonsteroidal anti-inflammatory drugs (NSAIDs, for example, celecoxib) when utilized to intercept colorectal neoplasia. However, low-baseline CVD risk or C-reactive protein level (a well-established marker of inflammation) eliminates this risk, highlighting, at the same time, the importance of a more personalized cancer interception. Interestingly, the use of antihypertensive drugs to reduce CVD is associated with toxicity risk, too. The general acceptance of this risk highlights the need to fill the gap between education on CVD risk reduction and education on cancer risk reduction. Another proposed reason behind the resistance to the idea of cancer interception is that. In contrast, CVD risk reduction treats well-known measurable conditions (such as hypertension and high cholesterol level) that can be followed to assess treatment effectiveness; actionable cancer drivers and prodromal conditions are less known by the general population. Actually, there is at least one good example of an actionable measurable condition for cancer, too: colorectal adenomas preceding colon cancer. Their number can be reduced by aspirin, which has been shown to decrease the incidence and mortality of colorectal cancer. Also, surgical control of colorectal adenomas can reduce cancer risk and mortality. Understandably, people struggle with treating or even curing cancer. However, cancer will never be controlled without prevention. This is why cancer interception is absolutely desirable and necessary. The disease is a leading cause of death. In 2020, it was responsible for nearly 10 million deaths worldwide.

Lung, colorectal, liver, stomach, and breast cancer accounted for half of these losses, and, unfortunately, new diagnoses were common. The new cases were 2.26 million for breast cancer, 2.21 million for lung cancer, 1.93 million for colorectal cancer, 1.41 million for prostate cancer, 1.20 million for skin cancer (non-melanoma), and 1.09 million for stomach cancer. In the last 40 years, while preventive risk reduction was contributing to the steady fall in heart disease death rates, cancer became the leading cause of death in many US states. In 1999, age-standardized heart disease mortality still was higher than that for cancer in all states, but in 2016 the situation was the opposite in 19 states. Age is among the most important cancer risk factors, and the world population is aging, reaching cancer-prone ages. Moreover, treatment improvement increased cancer patients’ lifespan, but survivors’ cancer risk is higher. This increasing cancer burden can only be tempered by an approach in which an increase in its interception parallels efforts in disease treatment. This second way is more cost-effective, counts fewer human costs, and will further reduce the burden of cancer on public health and wellbeing. To date, cancer prevention consists of interventions aimed at reducing generic external risk factors (such as smoking, alcohol, unhealthy diet, and radiation), and early detection. This approach is often perceived as a passive method requiring deprivation (from smoking, alcohol, some foods, and so on), and early detection can prevent cancer death but not cancer onset.

Moreover, people seek encouraging health information that could address cancer worries. That means that preventing cancer death (that is, the target of early detection) is not always the principal focus of people, who sometimes feel spontaneously compelled to take action rather than inaction against this disease. Today, it is possible to switch the focus from early cancer detection and reducing generic external risk factors to actionable cancer driver interception. Cancer Driver Interception refers to the idea of interrupting carcinogenesis at any point before the development of an invasive disease. In fact, cancer arises from a process of transformation of normal cells into cancer cells lasting years or decades; during this stage (the so-called prodromal phase) people are apparently healthy and totally asymptomatic, but several factors are actively driving this transformation process. And now we know that just like we can monitor hypertension, hypertriglyceridemia, obesity, and other risk factors that drive CVD development, cancer drivers are measurable, too. Once intercepted, actionable cancer drivers can be monitored, giving people feedback not only on the progression of the cancer prodromal phase but also on the effectiveness of the strategies (such as cancer chemoprevention, that is, the use of drugs, vitamins, or other agents to reduce the risk of cancer development) put in place to counteract their presence – just as in the case of people undergoing regular cholesterol test to evaluate cholesterol-reducing therapy efficiency.