Smart cancer nanomedicine

Abstract

Nanomedicines are extensively employed in cancer therapy. We here propose four strategic directions to improve nanomedicine performance and translation. (1) Patient stratification has become common practice in oncology drug development. Accordingly, probes and protocols for patient stratification are urgently needed in cancer nanomedicine, to identify individuals suitable for inclusion in clinical trials. (2) Rational drug selection is crucial for clinical and commercial success. Opportunistic choices based on drug availability should be replaced by investments in modular (pro)drug and nanocarrier design. (3) Combination therapies are the mainstay of clinical cancer care. Nanomedicines synergize with pharmacological and physical co-treatments, and should be increasingly integrated in multimodal combination therapy regimens. (4) Immunotherapy is revolutionising the treatment of cancer. Nanomedicines can regulate the behaviour of myeloid and lymphoid cells, thereby empowering anticancer immunity and immunotherapy efficacy. Alone and especially together, these four directions will fuel and foster the development of successful cancer nanomedicine therapies.

The solid progress of nanomedicine

“…The gradual implementation of universally standardized practices could promote more accurate reporting of materials and methodologies, and could change the paradigm for many nanotechnology products that already exist [41,42]. On top of this, improving the clinical impact of nanomedicines demands "smart thinking and rational and realistic reasoning," as stated by van der Meel et al in a recently published perspective article in Nature Nanotechnology [43]. In this sense, and particularly in the case of cancer therapy, patient stratification, rational drug selection, the use of combination therapies, and the targeting of the adaptive immune system are key for addressing scientific and medical questions that will potentiate the exploitation and, most importantly, the translation of nanomedicines into the clinic.…”

Challenges in nanomedicine clinical translation

“…Many new drug products that now appear on the market come with their own biomarker, and typically, these biomarkers are identified and evaluated early on in the developmental process. In this regard, one could even argue that biomarkers should already be identified before clinical development is commenced, and there is no reason why this-as for molecularly targeted therapeutic and monoclonal antibodies-should not also hold true for nanomedicinal drugs [6][7][8].…”

“…The observation that nanomedicines seem to be more prone to lack of predictability of patient benefit as compared with conventional drugs and molecularly targeted therapeutics may be due to the critical dependence of nanomedicine efficacy on pharmacokinetics, tissue distribution, target site accumulation and penetration, and drug release at the target site (and ideally in the target cell), which are all specific in vivo nanoparticulate performance aspects and which are very different in animal models versus in human patients. Lessons learnt in anticancer nanomedicine development have taught us the importance of tumor vascularization, stroma, and especially macrophage population in nanoparticle target localization and drug release, and these tissue morphology aspects typically vary dramatically inside a tumor, across tumors in a patient and even more so among (different cancerous lesions in) different patients [7][8][9]. This becomes all the more poignant when we realize that thus far, the (cancer) nanomedicine field has seen relatively little progress in the development of biomarkers and companion diagnostics.…”

Realizing Cancer Precision Medicine by Integrating Systems Biology and Nanomaterial Engineering

“…[111] In addition, a fundamental problem in successfully delivering nanocarriers to specific tumor sites in human patients is a lack of understanding of the EPR effect, which is observed in preclinical mouse models. [10,[112][113][114][115] In animal models of cancer, the EPR effect is thought to result from the tumor's induction of immature blood vessel formation, which causes nanoparticles to be accumulated in regions where the tumor is highly vascularized with immature vessels and where the vessels are more permeable. [11,116] However, in clinical trials with patients, numerous nanocarriers fail because of very low (less than 1%) accumulation in tumors.…”

“…Personalized nanomedicine is likely the future of nanomedicine, because this approach will take into account the heterogeneous characteristics of patients and, for cancer patients, the heterogeneity of cancer cells within a patient. [8][9][10] In the following two sections, we review how systems biology can contribute to realizing personalized nanomedicine by promoting EPR and aiding in target selection, and identifying treatment paradigms.…”