Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions.

The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family.

Targeting regulated cell death with plant natural compounds for cancer therapy: A revisited review of apoptosis, autophagy-dependent cell death, and necroptosis.

Regulated cell death (RCD) refers to programmed cell death regulated by various protein molecules, such as apoptosis, autophagy-dependent cell death, and necroptosis. Accumulating evidence has recently revealed that RCD subroutines have several links to many types of human cancer; therefore, targeting RCD with pharmacological small-molecule compounds would be a promising therapeutic strategy. Moreover, plant natural compounds, small-molecule compounds synthesized from plant sources, and their derivatives have been widely reported to regulate different RCD subroutines to improve potential cancer therapy. Thus, in this review, we focus on updating the intricate mechanisms of apoptosis, autophagy-dependent cell death, and necroptosis in cancer. Moreover, we further discuss several representative plant natural compounds and their derivatives that regulate the above-mentioned three subroutines of RCD, and their potential as candidate small-molecule drugs for the future cancer treatment.

CRISPR/Cas genome editing in triple negative breast cancer: Current situation and future directions.

Triple negative breast cancer (TNBC) has been well-known to be closely associated with the abnormal expression of both oncogenes and tumor suppressors. Although several pathogenic mutations in TNBC have been identified, the current therapeutic strategy is usually aimed at symptom relief rather than correcting mutations in the DNA sequence. Of note, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) has been gradually regarded as a breakthrough gene-editing tool with potential therapeutic applications in human cancers, including TNBC. Thus, in this review, we focus on summarizing the molecular subtypes of TNBC, as well as the CRISPR system and its potential applications in TNBC treatment. Moreover, we further discuss several emerging strategies for utilizing the CRISPR/Cas system to aid in the precise diagnosis of TNBC, as well as the limitations of the CRISPR/Cas system. Taken together, these findings would demonstrate that CRISPR/Cas system is not only an effective genome editing tool in TNBC, but a promising strategy for the future therapeutic purposes.