Unlocking the EGFR-mediated epitranscriptome: A pathway to novel therapies.

In this issue, Lv et al. explore EGFR-driven epitranscriptomic reprogramming in glioblastoma, revealing the pivotal role of the EGFR-ALKBH5-GCLM axis in ferroptosis protection. Their findings offer mechanistic insight and therapeutic strategies involving novel combination targets to enhance tumor responses.

Long Non-Coding RNAs as Emerging Targets in Lung Cancer.

Long non-coding RNAs (LncRNAs) are mRNA-like molecules that do not encode for proteins and that are longer than 200 nucleotides. LncRNAs play important biological roles in normal cell physiology and organism development. Therefore, deregulation of their activities is involved in disease processes such as cancer.

Dimeric p53 Mutant Elicits Unique Tumor-Suppressive Activities through an Altered Metabolic Program.

Unlabelled: Cancer-related alterations of the p53 tetramerization domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers, which are also normal p53 states under basal cellular conditions. However, their physiologic relevance is not well understood.

Omics analyses of a somatic breast cancer model identify cooperating driver events activating PI3K/AKT/mTOR signaling.

Alterations of the tumor suppressor , one of the most common events in cancer, alone are insufficient for tumor development but serve as drivers of transformation. We sought to identify cooperating events through genomic analyses of a somatic mouse model (equivalent to the hot spot mutation in human cancers) that recapitulates metastatic breast-cancer development. We identified cooperating lesions similar to those found in human breast cancers.

Differential Gain-of-Function Activity of Three p53 Hotspot Mutants In Vivo.

Unlabelled: The majority of TP53 missense mutations identified in cancer patients are in the DNA-binding domain and are characterized as either structural or contact mutations. These missense mutations exhibit inhibitory effects on wild-type p53 activity. More importantly, these mutations also demonstrate gain-of-function (GOF) activities characterized by increased metastasis, poor prognosis, and drug resistance.

p53 tetramerization: at the center of the dominant-negative effect of mutant p53.

The p53 tumor suppressor functions as a tetrameric transcription factor to regulate hundreds of genes-many in a tissue-specific manner. Missense mutations in cancers in the p53 DNA-binding and tetramerization domains cement the importance of these domains in tumor suppression. p53 mutants with a functional tetramerization domain form mixed tetramers, which in some cases have dominant-negative effects (DNE) that inactivate wild-type p53.