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    2020-08-30

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    Fig. 1. (A) MEDLINE PubMed was queried with “cancer therapeutics” (light blue diamonds). From 2008 to date, a steady growth has occurred, at an average annual growth rate (AAGR) of 3.9%. Over the same time period, MEDLINE PubMed was queried with a combination of “cancer therapeutics” and “nanotechnology” with the operator AND (orange squares). While the number of publications was much lower than that returned just querying with “cancer therapeutics”, it grew at an impressive AAGR of 55.3%. (B) The graph illustrates the number of entries in PubMed using “cancer diagnosis” as a search keyword (light blue diamonds, 31% AAGR) and “cancer diagnosis” in combination with “nanotechnology” with the operator AND (orange squares, 43% AAGR).
    and encourage development of novel tools for early recognition of cancer-specific molecular abnormalities before tumor formation.
    Recent applications of nano-biotechnology for early diagnostic and treatment of cancer provide a promising alternative to conven-tional therapeutics and treatments [5,6]. In fact, nanotechnology may offer innovative means to target chemotherapies selectively to cancer 1247819-59-5 [7], enable surgical resection of tumors quicker and more precisely and enhance the effectiveness of radiation-based therapies [8]. Over the past decade, large government funds for nanotechnology research have created some of the most sophisti-cated nanoscience laboratories in the world, and most of them have been engaged in developing innovative medicines to combat can-cer. Turning nanotechnology research into innovative solutions has led to an increasing number of cancer-related publications (4152 published documents with AAGR of 55.3%).
    Despite the recognition of the fact that early detection leads to improved outcome, better survival and lower cost, early cancer diagnostics have been largely overlooked in the healthcare sys-tem [9]. Traditionally, there have been many barriers in developing effective and reliable diagnostic assays. First, many tests do not give “yes” or “no” answers. Second, low-profit margins do not allow big companies to cover development costs. As such, the research field of cancer diagnostics has produced roughly 12,000 publica-tions between 2008–2018 (Fig. 1b) which is more than an order of magnitude lower than those published in the field of cancer ther-apeutics (Fig. 1a). Similarly, the number of publications describing the use of nanotechnology in cancer diagnostics (400; with a sig-nificant AAGR of 43%) has been much lower than those published on cancer therapeutics.
    Diagnostic vs. therapeutic nanotechnology: funding and industrial success
    The market of cancer pharmaceuticals is tightly dominated by the big companies. Priorities of these companies are given to amass-ing products and innovation through internal R&D, licensing, or acquisition [10]. This model consumes large economical resources but leads to frequent failures, and in most cases, efforts do not mate-rialize in drug approval. For example, in 2017 the whole oncology pipeline had over 600 molecules in late development stage, but only 22 drugs were approved by the Center for Drug Evaluation and Research (CDER) of the FDA in 2016. This is a major slowdown com-pared to the 45 new drugs in 2015 and 41 in 2014. Approved drugs also cost much more today than in the past decades. The budget for developing a successful drug can exceed $2.6 billion compared to $179 million in the seventies. Most drug candidates do not reach the market, and even already approved drugs are sometimes subject to
    failure. A 2009–2013 review by the European Medicines Agency showed that among 48 drugs approved for 68 indications, 39–57% did not show an improvement in survival or quality of life over placebo [11].
    In contrast to pharmaceutical industry, the diagnostics industry has a much lower risk/lower reward profile. Companies pro-filed in this market include Thermo Fisher Scientific Inc., Alere Inc., Biomerieux, Danaher Corporation, F. Hoffmann-La Roche AG, Becton Dickinson, Bio-Rad Laboratories, Bayer AG, Sysmex Corpo-ration, and Johnson & Johnson. Today’s diagnostic tests are accurate and less time consuming. In fact, some of them can be comfortably used at home without professional supervision (pregnancy test, blood glucose test and others).
    Unfortunately, in the last decades similar advances have not been made in the area of cancer diagnosis except for some progress in early detection of specific malignancies. To date, most studies have sought to identify tumor-specific antigens such as prostate specific antigen (PSA) as a marker for early diagnosis of prostate cancer. Identification of specific cancer biomarkers in blood plasma is a promising approach for early cancer detection. However, due to their low specificity and sensitivity, traditional tumor biomarkers alone or in combination with cancer detection models obtained by machine learning are still not available in clinic for cancer detection in general population [12]. This is the case, for exam-ple, for pancreatic ductal adenocarcinoma (PDAC), a tumor with high mortality [13]. Screening methods for early detection of PDAC and similar aggressive malignancies would enable identification of asymptomatic candidates, who could be promptly reported for diagnosis and treatment [14]. Screening may pave a way to radically limit the epidemiological impact of cancer by preventing or slow-ing down its progress through available interventions. Recently, the National Cancer Institute (NCI) has recognized that nano-based technologies may offer exciting opportunities, potentially becom-