Novel treatment strategies for brain tumors and metastases

Abstract

This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood-brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application.

Figure 1. Cross-section of a brain capillary, which represents the structure of the blood–brain barrier and brain–tumor barrier

The blood–brain barrier does not represent a distinct organ, but rather is a functional concept.

Figure 2. Primary brain tumor types

Reproduced with permission from [39] © Oxford University Press (2013).

Figure 3. Liposomes as a novel colloidal drug delivery system

Liposomes can be tailor-designed adopting diverse grafting strategies on its surface or modifications within the liposomal composition to provide tissue specificity, diagnosis and targetability.

Figure 4. Novel compounds for the treatment of brain tumors and metastases

(A) Benzimidazole thiophene compounds; (B) Di-hydro pyridine sulphonamides and di-hydro pyridine sulphamides derivatives; (C) Diphenylmethane derivatives; (D) Substituted pyrimidine compounds; (E) (4-Methoxy-phenyl)-methyl-(2-methyl-quinazolin-4-yl)-amine hydrochloride; (F) P97-Trastuzumab monoclonal antibody conjugate; (G) Trastuzumab-MCC-DM1 antibody-drug conjugate; (H) NKTR-102; (I) Taxane derivative; (J) KISS-1 polypeptides and nonpeptide water-soluble polymer conjugate (n = 2 to 4000); (K) HSP 90 inhibitor(s) containing fused amino pyridine core; (L) Cytidine analogs 5-aza-2′-deoxycytidine (decitabine); and (M) Tris(8-quinolinolato)gallium(III)).