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Summary: Cancer stem cells (CSCs) are documented to play a key role in tumorigenesis and therapy resistance. Despite significant progress in clinical oncology, CSC reservoirs remain elusive and difficult to eliminate. Reverse-turn peptidomimetics were characterized as disruptors of CBP/beta-Catenin interactions and represent a promising avenue to curb hyperactive canonical Wnt/beta-Catenin signaling in CSCs. Recent studies suggested Sam68 as a critical mediator of reverse-turn peptidomimetics response in CSC populations. Using computational and biochemical approaches we confirmed Sam68 as a primary target of reverse-turn peptidomimetics. Furthermore, we executed an in silico drug discovery pipeline to identify yet uncharacterized reverse-turn peptidomimetic structures displaying superior anti-CSC activity in transformed pluripotent and colorectal cancer cell models. Thus, we identified YB-0158 as a reverse-turn peptidomimetic small molecule with enhanced translational potential, altering key hallmarks of human colorectal CSCs in patient-derived ex vivo organoids and in vivo serial tumor transplantation.

Following the explosion of publications about COVID-19, some of these articles were retracted. These articles are potentially dangerous to public health as they can mislead about the nature of the virus. The growth and sensitive nature of retracted papers led to bibliometrics studies on them, although few, which focused more on the level of documents. This study, instead, examines the characteristics of the authors of these articles. 54 retracted COVID-19 articles that fit our study’s criteria were identified. The results revealed that 32% of these authors were MD, and about one-fifth of them had a past history of publishing retracted articles. The average number of authors per article was 6. Also, according to their profile in the Scopus, the mean number of documents, citations and their H-index were 61, 3159 and 12, respectively. Women also appeared in one-third of the articles as first and last authors. Continued research about retracted COVID-19 articles can continue to help prevent the further dissemination of questionable research findings.

Sam68 (Src associated in mitosis of 68 kDa) is an RNA-binding and multifunctional protein extensively characterized in numerous cellular functions, such as RNA processing, cell cycle regulation, kinase- and growth factor signaling. Recent investigations highlighted Sam68 as a primary target of a class of reverse-turn peptidomimetic drugs, initially developed as inhibitors of Wnt/β-catenin mediated transcription. Further investigations on such compounds revealed their capacity to selectively eliminate cancer stem cell (CSC) activity upon engaging Sam68. This work highlighted previously unappreciated roles for Sam68 in the maintenance of neoplastic self-renewal and tumor-initiating functions. Here, we discuss the implication of Sam68 in tumorigenesis, where central findings support its contribution to chromatin regulation processes essential to CSCs. We also review advances in CSC-targeting drug discovery aiming to modulate Sam68 cellular distribution and protein-protein interactions. Ultimately, Sam68 constitutes a vulnerability point of CSCs and an attractive therapeutic target to impede neoplastic stemness in human tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer incidence has increased in young adults over the last decade. Such a shift in epidemiology suggests increased environmental risk factors play a prominent role in the onset of the disease. DNA methylation is one of several aspects of the epigenome that are frequently mutated in cancer and that function in the silencing of endogenous viral repeats, also known as transposable elements. Here we discuss the findings from a recent mapping effort of Long Interspersed Nuclear Elements 1 (LINE1) transposition events over a lifetime in the colonic epithelium, which revealed increased levels of transposition in human colorectal tumors. These findings shed light on LINE1 retrotransposition in colorectal tumors and how it may be crucial in developing future therapeutic avenues. The frequency of somatic retrotranspositions of Long Interspersed Nuclear Elements 1 (LINE1) over a lifetime in healthy colonic epithelium and colorectal tumors has recently been reported. Indicative of a cell type-specific effect, LINE1 sequences in colonic epithelium showed lower levels of DNA methylation compared to other cell types examined in the study. Consistent with a role for DNA methylation in transposon silencing, the decreases in DNA methylation observed at LINE1 elements in colonic epithelium were accompanied by increases in LINE1 mRNA levels. In human primary colorectal tumors, LINE1 retrotransposition frequency was tenfold higher than in normal colonic tissues, with insertions potentially altering genomic stability and cellular functions. Here, we discuss the discoveries made by Nam and colleagues, emphasizing the intestinal-specific methylation signature regulating the LINE1 lifecycle and how this new information could shape future drug discovery endeavors against colorectal cancer. [ABSTRACT FROM AUTHOR]