On the need for the development of a cancer early detection, diagnostic, prognosis, and treatment response system

Cancer is the second leading cause of noncommunicable disease deaths in the world. In 2018, there were over 18 million new cancer cases and approximately 10 million people died from the disease globally. In 2019, almost two million new cases of cancer will be diagnosed in USA and over 600,000 people are expected to die from the disease. The incidence of cancer is expected to rise because of lifestyle changes and a rapidly aging population. Evidence suggests that early detection is critical to reducing cancer morbidity and mortality. In this paper, the development of an integrated smart wearable and biomarker detection system is proposed to help reduce cancer morbidity and mortality. The potential benefits and limitations of the system are discussed.


Discussion
More than any other factor, early detection (presymptomatic stage) is critical to arresting cancer due to progressive advancement in disease stage and metastasis. ISWEBDS could play a crucial role in early detection during the presymptomatic stage, reducing the morbidity, mortality and financial burden of the disease. It could play a key role in cancer prevention by detecting precursors of cancers or precancerous lesions, reducing the incidence of the disease. It could also be extremely useful in successful cancer treatment by providing insight into pharmacological responses or outcomes to therapeutic interventions. Indeed, changes in circulating DNA mutation patterns during cancer treatment typically indicate the appearance of resistant clones and it can be used to alter treatment strategy [55,57].
ISWEBDS can overcome the clinician's dependence on patient self-reporting for clinical decisions and it can cut out the need for regular onsite screening, which is necessary for detecting clinically relevant biomarkers. Thus, it will help in reducing cancer treatment costs by cutting expenditure on the regular conduct of laboratory diagnostic tests. ISWEBDS should make it easy to collect more reliable and responsive ratio-scaled outcome measures from patients remotely and in real time, reducing onsite follow-up and potentially increasing clinical trial recruitment and retention due to reduced cost and burden of travel.
Also, as ISWEBDS sends information to patients about their health status, it is likely to make them more informed about their activities and how it affects their health, causing them to make healthier choices. Indeed, research indicates that a well-informed patient is motivated to engage in healthy behavioral changes [58].
There are, however, some problems that must be overcome to make ISWEBDS a reality. In the last two decades, there have been rapid developments in the field of wireless body area networks [59], wearables, biosensors and bioelectronics [60][61][62][63][64]. In addition, although recent developments in biosensor technology have significantly improved the sensitivity of biomarkers in the early stages of cancer [65], challenges remain in biosensor technology, particularly in integration [66,67]. The invasive nature of the system is another limitation and biodegradable biosensors that are durable and programmable remotely will be the most effective way to make them work. Inflammation and subsequent OS from biosensor placement around tissues could lead to carcinogenesis. Biomarker sensitivity and specificity [68] is another problem that must be addressed to make the system a reality. Integrating the data from the biosensors to the wearable and knowing the precise level of a biomarker that should trigger an alert are challenges that must be overcome through research. The system might be costly, at least initially, making it out of reach for the poor, who might benefit the most from it. Also, placing biosensors in certain parts of the body, particularly in the lungs and the brain, is perhaps impractical, indicating that the system might be limited to certain areas of the body, potentially reducing its ability to detect cancers early in some parts of the body. Overdiagnosis, a key feature of both early detection and preventive screening [69], could also be a problem with the system. Table 2 below summarises the advantages and challenges of developing ISWEBDS.

Conclusion
The future of effective cancer treatment and management profoundly hinges upon the use of innovative methods, which will assist clinicians in disease management. An integrated system such as ISWEBDS will maximize the utility of biomarkers and the addition of biosensors and wearables will help in capturing labile biomarkers (biomarkers that are are liable to change or alteration and thus difficult to capture) in the cancer microenvironment. In addition, ISWEBDS could quickly determine the best treatment options, which is most likely to be successful reducing the problem of drug resistance. ISWEBDS can transform the problem of cancer by not only aiding in early detection, prevention, prognosis, recurrence and the prediction of treatment efficacy but also doing so at a Table 2. Advantages and challenges of integrated smart wearable and biomarker detection system.

Advantages
1. Early detection of cancer allowing for proper intervention and care and, reducing the mortality and morbidity of the disease 2. Aid in the prevention of cancers by detecting precancerous lesions 3. Used to predict treatment response and to alter treatment course, improving outcomes and saving lives 4. Overcomes clinician's dependence on patient self-reporting for clinical decisions and cuts out the need for regular onsite screening necessary for detecting biomarkers 5. Since it sends information to patients about their health status, it is likely to make them more informed about their activities and how it affects their health, causing them to make healthier choices Challenges 1. Specificity and sensitivity of biosensors to capture the targeted biomarkers 2. Individual variability of biomarker levels in the presence of cancer or in response to cancer treatment 3. Confounding results from biomarkers due to failure to identify factors that may alter the measurement of the biomarker including weight, age, gender, diet, other metabolic factors, and laboratory kits used 4. Engineering difficulty in transferring the biosensor capture information to the smart wearable 5. The cost of developing new biomarkers is high and this might be a problem, making the system out of reach for the most vulnerable people 6. Exact location to place the biosensor and problems of inflammation, pain and oxidative stress from tissue damage 7. The invasive nature of the system might limit its adoption Strategies to improve functionality 1. Investment in research to develop better biosensors that are highly sensitive and specific to certain biomarkers 2. Better collaboration between clinicians, funding agencies and the biotech industry 3. Subsidies and incentives from the government to spur research and development in biosensors, biomarkers and their integration 4. Development of biodegradable biosensors that will not induce inflammation and related problems 5. Development of less invasive methods of installing, replacing or removing biosensors fraction of the overall current cost and with great convenience for both patients and clinicians. It has the potential to revolutionize healthcare in this century by expanding the capabilities of the healthcare system, improving diagnostics and monitoring and the participation of patients in their wellbeing. However, significant collaboration would be necessary between clinicians, engineers and the biotechnology industry to make it a reality. Finally, early cancer detection does not necessarily translate to clinical benefits for patients and emphasis must equally be placed on early effective treatment following diagnosis to reduce the morbidity and mortality from the disease. In addition, although the article focuses on the use of ISWEBDS on cancers, it can be applied for the diagnosis, prediction, prognosis and treatment of any chronic disease.

Future perspective
The treatment of cancer currently involves different approaches including chemotherapy, radiotherapy, surgery and pharmacogenomics. Much effort has been expended on finding an outright cure to no avail and evidence suggests such a cure may never materialize in the near future. Consequently, the best way forward lies in early detection and ISWEBDS, if successfully developed, can play an important role in reducing the incidence and burden of cancers.

Executive summary
• Cancer is one of the leading causes of noncommunicable disease deaths in the world.
• Multiple lines of evidence indicate that early detection is critical to reducing the incidence and burden of the disease. • In this paper, an integrated smart wearable and biomarker detection system (ISWEBDS) to help in the early detection, prognosis, diagnosis and treatment of cancer is proposed. • ISWEBDS has the potential to revolutionize healthcare in this century by expanding the capabilities of the healthcare system, improving diagnostics and monitoring and the participation of patients in their wellbeing.

Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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