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Bioorthogonal technique adds azide groups to cancer cell surfaces for selective drug targeting

The USPTO’s Patent Trial and Appeal Board has ruled in favor of the Broad Institute of MIT and Harvard retaining intellectual property rights covered by its patents for CRISPR gene-editing...

Researchers employ an engineered microbe to destroy tumor cells in mice.

A potent synthetic inorganic antibiotic with activity against drug-resistant pathogens

Scientific Reports, Published online: 6 February 2017; doi:10.1038/srep41999

Big science has a buzzword problem

Nature 541, 7638 (2017). http://www.nature.com/doifinder/10.1038/541450a

Author: Megan Scudellari

Moonshots, road maps, frameworks and more are proliferating, but few can agree on what these names even mean.

Researchers find diverse ways that the molecules can regulate cancer’s spread.

Five big mysteries about CRISPR’s origins

Nature 541, 7637 (2017). http://www.nature.com/doifinder/10.1038/541280a

Author: Heidi Ledford

Where did it come from? How do organisms use it without self-destructing? And what else can it do?

An initiative to replicate key findings in cancer biology yields a preliminary conclusion: it’s difficult.

A cell phone–based microscope can identify mutations in tumor tissue and image products of DNA sequencing reactions.

Related Articles

Glycan Alteration Imparts Cellular Resistance to a Membrane-Lytic Anticancer Peptide.

Cell Chem Biol. 2017 Feb 16;24(2):149-158

Authors: Ishikawa K, Medina SH, Schneider JP, Klar AJ

Abstract
Although resistance toward small-molecule chemotherapeutics has been well studied, the potential of tumor cells to avoid destruction by membrane-lytic compounds remains unexplored. Anticancer peptides (ACPs) are a class of such agents that disrupt tumor cell membranes through rapid and non-stereospecific mechanisms, encouraging the perception that cellular resistance toward ACPs is unlikely to occur. We demonstrate that eukaryotic cells can, indeed, develop resistance to the model oncolytic peptide SVS-1, which preferentially disrupts the membranes of cancer cells. Utilizing fission yeast as a model organism, we show that ACP resistance is largely controlled through the loss of cell-surface anionic saccharides. A similar mechanism was discovered in mammalian cancer cells where removal of negatively charged sialic acid residues directly transformed SVS-1-sensitive cell lines into resistant phenotypes. These results demonstrate that changes in cell-surface glycosylation play a major role in tumor cell resistance toward oncolytic peptides.

PMID: 28089756 [PubMed - indexed for MEDLINE]

Magnesium silicide particles can react with oxygen in acidic tumor environments

Greater control is desirable in the stochastic conjugation technology used to synthesize antibody–drug conjugates (ADC). We have shown recently that a fluorescent dye can be stably conjugated to a mAb using a bifunctional platinum(II) linker. Here, we describe the general applicability of this novel linker technology for the preparation of stable and efficacious ADCs. The ethylenediamine platinum(II) moiety, herein called Lx, was coordinated to Desferal (DFO) or auristatin F (AF) to provide storable “semifinal” products, which were directly conjugated to unmodified mAbs. Conjugation resulted in ADCs with unimpaired mAb-binding characteristics, DAR in the range of 2.5 to 2.7 and approximately 85% payload bound to the Fc region, presumably to histidine residues. To evaluate the in vivo stability of Lx and its effect on pharmacokinetics and tumor targeting of an ADC, Lx-DFO was conjugated to the HER2 mAb trastuzumab, followed by radiolabeling with 89Zr. Trastuzumab-Lx-DFO-89Zr was stable in vivo and exhibited pharmacokinetic and tumor-targeting properties similar to parental trastuzumab. In a xenograft mouse model of gastric cancer (NCI-N87) or an ado-trastuzumab emtansine-resistant breast cancer (JIMT-1), a single dose of trastuzumab-Lx-AF outperformed its maleimide benchmark trastuzumab-Mal-AF and FDA-approved ado-trastuzumab emtansine. Overall, our findings show the potential of the Lx technology as a robust conjugation platform for the preparation of anticancer ADCs. Cancer Res; 77(2); 257–67. ©2016 AACR.

Abstract

As cells turn cancerous, ribosome regulators force the cellular machines to preferentially produce cancer proteins

Researchers attempt to estimate how much of the human genome’s methylation patterns can be attributed to genetic ancestry.

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Therapeutic Efficacy of a Family of pHLIP-MMAF Conjugates in Cancer Cells & Mouse Models.

Mol Pharm. 2017 Jan 03;:

Authors: Burns KE, Hensley H, Robinson MK, Thévenin D

Abstract
The targeting of therapeutics specifically to diseased tissue is crucial for the development of successful cancer treatments. The approach here is based on the pH(Low) Insertion Peptide (pHLIP) for the delivery of a potent mitotic inhibitor monomethyl auristatin F (MMAF). We investigated, six pHLIP variants conjugated to MMAF to compare their efficacy in vitro against cultured cancer cells. While all pHLIP-MMAF conjugates exhibit potent pH- and concentration-dependent killing, their cytotoxicity profiles are remarkably different. We also show that the lead conjugate exhibits significant therapeutic efficacy in mouse models without overt toxicities. This study confirms pHLIP-monomethyl auristatin conjugates as possible new therapeutic options for cancer treatment and supports their further development.

PMID: 28048942 [PubMed - as supplied by publisher]

Abstract

Selected quotes from an eventful year

Newly discovered CasX and CasY enzymes could be a safety net for UC Berkeley in an ongoing patent dispute

The gene-editing technology mutates the virus’s DNA, blocking its replication in immune cells

In his first inaugural address, U.S. President Obama said, “We'll restore science to its rightful place…” He subsequently used this phrase to frame a number of activities across his administration.* While I, like many in the scientific community, was pleased with this declaration, I found the term “rightful place” to be thought-provoking. Author: Jeremy Berg

New approaches to treating cancer have shown great promise, but they also come with serious risks that give us cause for concern.