Cross-species analysis of SHH medulloblastoma models reveals significant inhibitory effects of trametinib on tumor progression.

Sonic Hedgehog (SHH) medulloblastomas (MBs) exhibit an intermediate prognosis and extensive intertumoral heterogeneity. While SHH pathway antagonists are effective in post-pubertal patients, younger patients exhibit significant side effects, and tumors that harbor mutations in downstream SHH pathway genes will be drug resistant. Thus, novel targeted therapies are needed.

Folic Acid-Functionalized Nanomedicine: Folic Acid Conjugated Copolymer and Folate Receptor Interactions Disrupt Receptor Functionality Resulting in Dual Therapeutic Anti-Cancer Potential in Breast and Prostate Cancer.

We have previously reported on a functionalized folic acid (FA) conjugated poly(styrene--maleic anhydride) (SMA) via biological linker 2,4-diaminobutyric acid (DABA) (FA-DABA-SMA) copolymer. This biocompatible nanocopolymer self-assembles in a pH-dependent manner, providing stimuli responsiveness, active targeting, and extended release of hydrophobic chemotherapeutic agents and effectively penetrates the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased tumor spheroid volume, revealing a previously unknown mechanism of action.

Next-Generation Multimodality of Nanomedicine Therapy: Size and Structure Dependence of Folic Acid Conjugated Copolymers Actively Target Cancer Cells in Disabling Cell Division and Inducing Apoptosis.

Nanomedicine as a multimodality treatment of cancer utilizes the advantages of nanodelivery systems of drugs. They are superior to the clinical administration of different therapeutic agents in several aspects, including simultaneous delivery of drugs to the active site, precise ratio control of the loading drugs and overcoming multidrug resistance. The role of nanopolymer size and structural shape on the internalization process and subsequent intracellular toxicity is limited.

Recent advances in "smart" delivery systems for extended drug release in cancer therapy.

Advances in nanomedicine have become indispensable for targeted drug delivery, early detection, and increasingly personalized approaches to cancer treatment. Nanoparticle-based drug-delivery systems have overcome some of the limitations associated with traditional cancer-therapy administration, such as reduced drug solubility, chemoresistance, systemic toxicity, narrow therapeutic indices, and poor oral bioavailability. Advances in the field of nanomedicine include "smart" drug delivery, or multiple levels of targeting, and extended-release drug-delivery systems that provide additional methods of overcoming these limitations.

Agonist-Biased Signaling via Matrix Metalloproteinase-9 Promotes Extracellular Matrix Remodeling.

The extracellular matrix (ECM) is a highly dynamic noncellular structure that is crucial for maintaining tissue architecture and homeostasis. The dynamic nature of the ECM undergoes constant remodeling in response to stressors, tissue needs, and biochemical signals that is are mediated primarily by matrix metalloproteinases (MMPs), which work to degrade and build up the ECM. Research on MMP-9 has demonstrated that this proteinase exists on the cell surface of many cell types in complex with G protein-coupled receptors (GPCRs), and receptor tyrosine kinases (RTKs) or Toll-like receptors (TLRs).

Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core.

Engineering of a "smart" drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a "smart" drug delivery system to be specific for a tumour in vivo and to penetrate the inner core remains a major design challenge.