Rakhi Mishra

ASK1 Signaling in Cancer: Pathogenic Driver or Therapeutic Target?

ABSTRACT Apoptosis signal‐regulating kinase 1 (ASK1), an important member of the MAP kinase kinase kinase (MAP3K), has been identified as a significant modulator of cellular responses to oxidative stress, inflammatory responses, and endoplasmic reticulum stress. Structurally characterized by its thioredoxin‐binding domain, its kinase domain, and coiled‐coil structures, ASK1 relays downstream stimulation of JNK and p38 MAPK cascades. Yet, its role in cancer function is paradoxical and simultaneously serves as both a cancer inhibitor and an activator rely on cellular settings. In this article, an overview of the molecular biology of ASK1 is presented with emphasis on the elusive balance between stimulation and suppression by upstream molecules such as Trx, TRAF proteins, and ubiquitination machinery. We provide an overview of the dualistic role of ASK1 in cancer pathophysiology showing how its dysregulation leads to tumor development, metastasis, chemoresistance, or tumor suppression by pro‐apoptotic signals, respectively. An example of context‐dependent action is provided using the examples of different cancers including lung, breast, ovarian, and hepatocellular carcinoma. Moreover, we discuss new therapeutic approaches to ASK1 such as small‐molecule inhibitors, RNA therapies, and protein‐protein interaction modulation and speculate on their potential in personalized medicine. The article also deals with future opportunities in the sense of the bivalent character of ASK1 in developing context‐dependent and targeted cancer therapies. The key to unlocking the potential of ASK1 to be used as a therapeutic intervention and overcome the complications that are posed by its dualistic nature in cancer biology lie in the understanding of the complex regulatory network it forms.

Acyl Urea Compounds Therapeutics and its Inhibition for Cancers in Women: A Review

Acyl urea compounds have garnered significant attention in cancer therapeutics, particularly for their potential effectiveness against cancers that predominantly affect women, such as breast and ovarian cancers. The paper presents a report on the investigation of acyl urea compounds that are reported to involve a multi-faceted approach, including synthetic chemistry, biological assays, and computational modeling. A wealth of information on acyl urea and its purported effects on cancer affecting women has been gathered from different sources and condensed to provide readers with a broad understanding of the role of acyl urea in combating cancer. Acylureas demonstrate promising results by selectively inhibiting key molecular targets associated with cancer progressions, such as EGFR, ALK, HER2, and the Wnt/β-catenin signaling pathway. Specifically, targeting acyl ureas impedes tumor proliferation and metastasis while minimizing harm to healthy tissues, offering a targeted therapeutic approach with reduced side effects compared to conventional chemotherapy. Continued research and clinical trials are imperative to optimize the efficacy and safety profiles of acylurea-based therapies and broaden their applicability across various cancer types. Acyl urea compounds represent a promising class of therapeutics for the treatment of cancers in women, particularly due to their ability to selectively inhibit key molecular targets involved in tumor growth and progression. The combination of synthetic optimization, biological evaluation, and computational modeling has facilitated the identification of several lead compounds with significant anticancer potential. This abstract explores the therapeutic mechanisms and targeted pathways of acyl ureas in combating these malignancies, which will be useful for future studies.