Expanding the nanotherapeutic toolbox for non-small-cell lung cancer

The effectiveness and tolerability of a cancer-directed medication often depend on the vehicle in which is delivered. Paclitaxel, one most common chemotherapies administered to patients with non-small-cell lung cancer (NSCLC), traditionally polyoxyethylated castor oil Cremophor EL, associated frequent hypersensitivity reactions. Accumulation paclitaxel itself outside tumors also results side-effects such as neutropenia neuropathy.1Wood A.J.J. Rowinsky E.K. Donehower R.C. Paclitaxel (Taxol).N Engl J Med. 1995; 332: 1004-1014Crossref PubMed Scopus (1891) Google Scholar Nanotherapeutic delivery systems have potential reduce medication-related toxicity off-target effects.2Shi J. Kantoff P.W. Wooster R. Farokhzad O.C. Cancer nanomedicine: progress, challenges opportunities.Nat Rev Cancer. 2017; 17: 20-37Crossref (2573) Nanotherapies benign surface properties can encapsulate medications, removing need for solvents EL. Even without specific target ligands, nanotherapeutic macromolecules may accumulate solid due cancer's increased vasculature permeability decreased resorption into blood lymph vessels.3Matsumura Y. Maeda H. A new concept macromolecular therapeutics chemotherapy: mechanism tumoritropic accumulation proteins antitumor agent smancs.Cancer Res. 1986; 46: 6387-6392PubMed Since Food Drug Administration approval liposomal doxorubicin 1995, number promising nanotherapy trials subtly changed landscape tumor treatment.2Shi In NSCLC, has allowed administration at higher concentrations fewer (Figure 1). 2012, albumin-bound (nab-paclitaxel) was shown phase III trial favorable response rate compared solvent-based when combined carboplatin, less neuropathy.4Socinski M.A. Bondarenko I. Karaseva N.A. et al.Weekly nab-paclitaxel combination carboplatin versus plus first-line therapy advanced cancer: Final trial.J Clin Oncol. 2012; 30: 2055-2062Crossref (536) Although no survival benefit seen cohort whole, aged over 70 years had prolonged overall nab-paclitaxel, possibly better drug tolerability. Polymeric micelles been long recognized system hydrophobic antineoplastics. Because they self-assemble from block polymers, these be tailored variety passenger molecules, sizes, stabilities diverse biological environments.5Miyata K. Christie R.J. Kataoka nano-scale delivery.React Funct Polym. 2011; 71: 227-234Crossref (322) 2007, II Korea showed that 26 69 (37.7%) radiographic Genexol®-PM, polymeric micelle formulation paclitaxel, cisplatin, side-effect profile.6Kim D.W. Kim S.-Y. H.-K. al.Multicenter Genexol-PM, novel Cremophor-free, cisplatin cancer.Ann 2007; 18: 2009-2014Abstract Full Text PDF (256) However, subsequent Genexol®-PM gemcitabine clinical activity against but high rates anemia high-grade neutropenia.7Ahn H.K. Jung M. Sym S.J. al.A Cremorphor EL-free (Genexol-PM) non-small cell cancer.Cancer Chemother Pharmacol. 2014; 74: 277-282Crossref (109) Overall, high-quality evidence comparing micelle-formulated Cremophor-based treatment human NSCLC lacking. this issue Annals Oncology, Shi al. present randomized, 454-patient, (pm-Pac) standard metastatic setting.8Shi Gu A. Huang C. al.Comparing nanoparticle micellar an open-label, multicenter, trial.Ann 2020; 32: 85-96Abstract (4) study achieved its primary endpoint, showing statistically significant difference objective between pm-Pac arm (50%) (26%). not adequately powered detect survival, authors note longer progression-free 50% lower severe adverse effects group receiving pm-Pac. Of interest, did appear age, both above below age 60 benefit. These are encouraging although it remains whether, follow-up, pm-Pac-based regimens lead survival. It unknown whether benefits will demonstrated other antineoplastics immunotherapies, now commonly used conjunction cytotoxic chemotherapy NSCLC.9Socinski Jotte R.M. Cappuzzo F. al.Atezolizumab nonsquamous NSCLC.N 2018; 378: 2288-2301Crossref (1542) Scholar, 10Paz-Ares L. Luft Vicente D. al.Pembrolizumab squamous cancer.N 379: 2040-2051Crossref (1398) 11Gandhi Rodríguez-Abreu Gadgeel S. al.KEYNOTE 189 (adeno): Pembrolizumab (carbo/pemetrexed) non–small-cell (adeno).N 2078-2092Crossref (2556) contrast, safety efficacy immunotherapy established, least now.12West McCleod Hussein alone non-squamous (IMpower130): multicentre, randomised, 3 trial.Lancet 2019; 20: 924-927PubMed (445) their discussion, further optimization studied regimen, inclusion maintenance therapy, could enhance advantages albumin-based smaller size, leading greater penetration. Without directly two, still theoretical. Nonetheless, presented by suggest therapeutic option NSCLC. welcome news field nanotechnology nanotherapeutics through proof using nanoparticles vehicles bringing medications cells. provides second addition solvent-related versatility, chemotherapy13Lv Tang Z. Li al.Co-delivery PEG-polypeptide nanovehicle cancer.Biomaterials. 35: 6118-6129Crossref (247) targeted based cancer-specific ligands.14Hrkach Von Hoff Ali M.M. al.Preclinical development translation PSMA-targeted docetaxel differentiated pharmacological profile.Sci Transl 4: 128ra39Crossref (820) ubiquity growing knowledge biophysical many cancers future opportunity improve way we treat cancer. Pm-Pac just first therapies show results.