The Ink4a/Arf locus encodes two distinct proteins, both of which may contribute to senescence and tumor suppression. We find that human diploid fibroblasts (HDFs) that are specifically deficient for p16INK4a achieve anchorage independence when transduced with retroviruses encoding telomerase (hTERT) and either Ras or Myc. Significantly, Ras and Myc together enable the cells to form tumors in nude mice but at a frequency that suggests additional genetic changes. All five tumors analyzed expressed high levels of Ras and retained functional p53, although two showed downregulation of Arf. Cytogenetic analyses identified clonal chromosomal alterations that may have contributed to tumorigenesis, but the tumor cells were essentially diploid.
The Rappaport Faculty of Medicine and Research Institute, and the Rappaport Technion Integrated Cancer Center (R-TICC), Technion-Israel Institute of Technology, Haifa 3109601, Israel.
Cytokines constitute a family of proteins that modulate the immune system and are secreted by many cells. CXCL12, along with its receptor CXCR4, are essential players in numerous processes. Dysregulation of their function underlie the mechanism(s) of several pathologies, including malignancies.
Targeted protein degradation (TPD) represents an innovative therapeutic strategy that has garnered considerable attention from both academic and industrial sectors due to its promising developmental prospects. Approximately 85% of human proteins are implicated in disease pathogenesis, and the FDA has approved around 400 drugs targeting these disease-related proteins, predominantly enzymes, transcription factors, and non-enzymatic proteins. However, existing therapeutic modalities fail to address certain "high-value" targets, such as c-Myc and Ras.
Background And Introduction: Two and half percent of the Indian population suffer from gallbladder cancer (GBC). The primary factors that lead GBC are associated with mutation of several protooncogenes such as EGFR, ERBB2, Myc, and CCND1 along with dysregulation of several tumor suppressor genes such as SMAD4 and CDKN2A. Bacterial infection caused by S.
Alteration or abnormal activation of RTKs have been recurrently observed and recognized as an important driving factor in the progression of many human cancers. Ferroptosis, an iron-dependent form of regulated necrosis triggered by the accumulation of lethal lipid peroxides on cell membranes, has been implicated in various tumor types. Here we reported that oncogenic RTKs/RAS/RAF/c-Myc axis promotes cancer cells to ferroptosis.
The multi-selective tri-complex RAS(ON) inhibitors RMC-7977 and RMC-6236 signal new avenues for RAS targeting. This systematic review aims to comprehensively present the available preclinical and early clinical data on these agents. We screened Medline, Scopus, the ESMO and ASCO conference sites and ClinicalTrials.
