Precision nanomedicine in cancer: how far are we from personalization?

KEYWORDS:

• Cancer
• nanotechnology
• nanomedicine
• precision medicine
• nanodiagnostics

Precision nanomedicine in cancer

Nanotechnology has been continuously challenging the way we perceive diagnostics and therapy, and therefore impacting the way we diagnose, image, and treat cancer [1]. Novel concepts are continuously arising that show promise to deliver one or more treatment solutions to a specific type of cancer and doing so by simultaneously allowing visualization of the therapeutic effects [2,3]. These solutions have demonstrated the application of a multitude of nanoscale devices and platforms that make use of information retrieved from each subgroup of molecular biomarkers to direct treatment in a more precise and selective strategy. Such nanomedicines have changed the way we manage cancer by: (i) focusing on early detection of malignancy, even at the molecular level; (ii) new imaging schemes for real-time assessment of therapeutics; (iii) multifunctional therapeutics, where multiple functional/therapeutic moieties have been loaded into nanoscale devices to allow selective targeting, signaling, and delivery with improved precision and specificity to tumors; (iv) incorporating relevant biomarker information retrieved from the target patient onto the nanomedicine for personalization [4–6].

Precision nanomedicine has profited from the tremendous amount of information retrieved from big data screening that put forward selective biomarkers that allow focusing on a particular type of target [7]. In fact, most of the identified biomarkers have been used in the assembly of very specific and dedicated nanoscale devices, thus enhancing the precise targeting of a particular cell and/or tissue. Conversely, gathering the necessary data for these big data screening efforts has also profited from nanotechnology-designed molecular diagnostics that provide multiplexing and high throughput while reducing the amount of sample needed and associated costs [8]. Such endeavors have also allowed the identification of biomarkers before onset of disease, which in turn enhance the performance of prediction algorithms that evaluate risk and predisposition to cancer. It should also be referred that nanotechnology-based diagnostics have been developed toward point-of-care screening and analysis, thus shifting from invasive biopsies and traditional blood tests toward less invasive biological samples, e.g. saliva and urine.

Nanomedicines used for theranostics (diagnostics and therapy) have relied on the remarkable properties conveyed by nanomaterials to provide more precise tracking of therapeutics and diagnostics within the body that can be accomplished with minimal invasion and using both standard and new disruptive approaches. Some of these nanotheranostics medicines may use the information retrieved from biomarker characterization and assortment to become active-response precise treatment solutions, i.e. responsive materials that react to a particular cell, tissue, and/or metabolic microenvironment to deliver treatment with improved precision. Two main strategies have been followed: (i) responsive conjugates that release the therapeutic cargo at selected precise locations as a response to sensing of the local environment (e.g. pH-based release, enzyme degradation of encapsulating formulation, etc.); or (ii) nanoscale carriers that can be imaged by the clinician who is then able to actuate upon them once they reach a precise site. Both show tremendous promise in the lab and their particular niches, but only but a few have been exposed to the real world and effectively transposed into the clinics [9,10].

Personalization of precision nanomedicines in cancer. Is it time yet?

Nanotechnology has clearly revolutionized the way we see cancer diagnostics and treatment. Perhaps the most important feature is the possibility for highly precise delivery of therapeutics that improve drug/treatment efficacy while simultaneously providing information on biodistribution or of a specific micro environment condition [11,12]. Having said that, one should look into the process of biomarker characterization and tailoring of those nanomedicines to the individual (e.g. mutation pattern, hormone receptor, miRNAs profile, etc.), providing in fact for individualized and personalized medicine. Such characterization is made possible via current high throughput parallel diagnostics platforms capable of an integrated interpretation of data arising from genomic profiling, transcriptomics, and metabolomics that provide massive amount of data on an individual’s molecular phenotype. Incorporation of this information into a single therapeutic device is not trivial. Such comprehensive incorporation of combinatory nanomedicines are not easily attained and are still more of a theoretical concept rather than effective devices [13].

It is foreseen that personalization of precision nanomedicine focus on the use of combinatory strategies that put together converging therapy avenues originating from the individual’s molecular signature. In fact, current cancer treatment regimens use this combinatory approach and molecular profiling of individual biomarkers to tailor therapeutic options in a more effective way. For example, combined use of drugs based on genetic profiling are key aspects of successful therapy in current anti-cancer protocols. This approach requires high throughput simple rapid and cheap DNA sequencers [8]. The disruptive aspect of nanomedicines is the possibility of combining these different elements onto a single nanoscale platform that additionally provides for means to evaluate therapy efficacy in real time, thus allowing for even more precise drug administration. What is more, because some of these nanomedicines may be constituted by several monomers, a specific, personalized therapeutic regimen may be elaborated that mirrors the individual’s molecular profile [14,15].

Nevertheless, this personalized precision (nano)medicine is still far from the clinics. Despite all current efforts, the issue of real hierarchization of biomarkers, derived from the tremendous heterogeneity of cancer not only between individuals but throughout cancer development in each organism, is still a real bottleneck. Perhaps the idea of personalizing medicine is still nothing more than a vision, and the real concept is reinforcing and optimizing the precision of current nanomedicines. Most of these precision nanomedicines are trialed in mouse models and translation to humans is far from trivial. But some solutions may derive from setting up fast processes to assess efficacy using cell models retrieved directly from the patients, who would then receive a more tailored version of the precision nanomedicines [16]. Also, there is still plenty to be done toward effective toxicological evaluation of these nanomedicines, particularly due to the lack of regulatory pathways and standardization for materials characterization, biological assays, etc. In fact, there is still a huge gap between the developments in the lab and proposed conceptual nanotherapeutics, and the effective translation into clinically efficient nanomedicines that may be of use to the public. Some of these issues are intrinsic to the nanomaterial/nanoparticle, such as physical and chemical characterization, influence of the biology of the organism on the nanomedicine, critical evaluation of pharmacokinetics and pharmacodynamics; and extrinsic to the nanodevices, including the regulatory definition and pathway to approval, financial impact on the health systems, and the possible distortion in social and economic access to these radical new approaches [17].

Precision nanomedicine in cancer is here to stay. More and more clinicians will rely on biomarker data to convey personalized decision on cancer treatment, which will be made taking into account the available selective therapeutics. But this comes with a cost; some rare profiles might become orphans in terms of available precision nanomedicines since these will target those profiles already proven to work. Nevertheless, since more and more information will be available, personalized action using nanomedicines will become standard issue in tackling specific cancers.

Declaration of interest

PV Baptista is an Associate Professor at Universidade NOVA de Lisboa. The author acknowledges financial support from FCT/MEC through Project UID/Multi/04378/2013. The author has no other 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 apart from those disclosed.

Additional information

Funding

The author acknowledges financial support from FCT/MEC [Project UID/Multi/04378/2013].