Highlights of This Issue Free

Tumor recurrence remains a challenging issue for the treatment of cancer. Sustained clinical response may require therapeutics that attack tumor-initiating cells (TIC), which may not be effectively targeted by conventional antitumor therapies. In this article, Sapra and colleagues report the development of a novel antibody-drug conjugate (ADC) that targets the TIC-associated antigen 5T4. In preclinical studies, the anti-5T4 ADC was shown to eradicate tumors in xenograft models with low to moderate 5T4 expression levels. The conjugate has the potential to be efficacious in multiple tumor indications, including non-small cell lung cancer and breast cancer.

SS1P is a recombinant immunotoxin that targets and kills mesothelin-expressing cancer cells. It has modest activity in humans, because immunogenicity limits the number of doses that can be given, and capillary leak syndrome limits the amount that can be given. Weldon and colleagues describe a redesigned variant of SS1P that produces complete regressions of mesothelin-expressing tumors growing in mice. In humans, the redesigned immunotoxin is predicted to trigger a reduced immunogenic response and reduced capillary leak syndrome, allowing treatment with more and higher doses of the therapeutic agent. These features should result in improved antitumor activity.

Metastatic triple negative breast cancer (mTNBC) is an aggressive form of breast cancer with limited treatment options. Craig and colleagues conducted whole genome and transcriptome sequencing in mTNBC within the context of a clinical feasibility study whose objective was to search for therapeutically actionable genomic alterations for informing molecularly guided treatment recommendations. In addition to providing a view of the somatic landscape of these tumors, their study provides evidence for relevant molecular contexts of vulnerability in some mTNBC, particularly those related to inhibition of the PI3K/AKT/MTOR and/or RAS/RAF/MEK/ERK pathways.