A pan-KRAS degrader for the treatment of KRAS-mutant cancers.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants.

Preclinical evaluation of Ga-labeled peptide CK2 for PET imaging of NRP-1 expression in vivo.

Purpose: Neuropilin-1 (NRP-1) is a multifunctional protein involved in a variety of biological processes such as angiogenesis, tumorigenesis and immunomodulation. It was usually overexpressed in many cancer cell lines and correlated with poor prognosis of breast cancer. Positron emission tomography (PET) is an advanced imaging technique for detecting the function and metabolism of tumor-associated molecules in real time, dynamically, quantitatively and noninvasively.

Automated Synthesis and Preclinical Evaluation of Optimized Integrin α6-Targeted Positron Emission Tomography Imaging of Pancreatic Cancer.

Integrin α6 has been considered a promising biomarker, is overexpressed in many tumors, and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we identified a novel high-affinity integrin α6-targeted peptide named RD (Arg-Trp-Tyr-Asp-PEG4)-Lys-Lys and developed a F-radiolabeled peptide tracer ([F]-AlF-NOTA-RD) and evaluated its potential application in positron emission tomography (PET) imaging of pancreatic cancer. [F]-AlF-NOTA-RD was produced using GMP (Good Manufacturing Practice of Medical Products)-compliant automatic radiosynthesis on a single GE FASTLab2 cassette-type synthesis module.

EDB-FN targeted probes for the surgical navigation, radionuclide imaging, and therapy of thyroid cancer.

Purpose: Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp (AVRTSAD) and developed three EDBp-based probes, Cy5-PEG4-EDBp(Cy5-EDBp), [F]-NOTA-PEG4-EDBp([F]-EDBp), and [Lu]-DOTA-PEG4-EDBp ([Lu]-EDBp), for the surgical navigation, radionuclide imaging, and therapy of TC.

Methods: Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy.

Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach.

Effectively killing pathogenic bacteria is key for the treatment of sepsis. Although various anti-infective drugs have been used for the treatment of sepsis, the therapeutic effect is largely limited by the lack of a specific bacterium-targeting delivery system. This study aimed to develop antibacterial peptides that specifically target pathogenic bacteria for the treatment of sepsis.

Sodium Pump Na + /K + ATPase Subunit α1-Targeted Positron Emission Tomography Imaging of Hepatocellular Carcinoma in Mouse Models.

Purpose: Positron emission tomography (PET) imaging was not efficiently used in the early diagnosis of hepatocellular carcinoma (HCC) due to the lack of appropriate tracers. Sodium pump Na + /K + ATPase subunit α1 (NKAα1) emerges to be a potential diagnostic biomarker of HCC. Here, we investigated the feasibility of F-ALF-NOTA-S3, a PET tracer based on an NKAα1 peptide, to detect small HCC.

Integrin α6-Targeted Magnetic Resonance Imaging of Hepatocellular Carcinoma in Mice.

Purpose: Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA) based on the integrin α6-targeted RWY peptide that we previously identified to detect HCC.

Integrin α6-Targeted Positron Emission Tomography Imaging of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin α6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin α6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics.

Integrin α6 targeted positron emission tomography imaging of hepatocellular carcinoma in mouse models.

Integrin α6 emerges to be a diagnostic biomarker for hepatocellular carcinoma (HCC). Here, we translated our previously identified integrin α6 targeted peptide RWY into a positron emission tomography (PET) tracer F-RWY for the detection of HCC lesions in following four HCC mouse models including subcutaneous, orthotopic, genetically engineered and chemical induced HCC mice. F-RWY produced high PET signals in liver tumor tissues that were reduced by blocking studies using nonradiolabeled RWY peptide.

Identification of a sodium pump Na/K ATPase α1-targeted peptide for PET imaging of breast cancer.

The sodium pump Na/K ATPase a1 subunit(NKA a1), an attractive cancer-related biomarker and therapeutic target, is closely related to the development and progression of several cancers including breast cancer. Currently, a NKA a1 inhibitor, UNBS1450, has already evidenced its great therapeutic potential in personalized cancer treatment. The ability of non-invasive imaging of NKA a1 expression would be useful for selecting cancer patients who may benefit from this drug.