How do you create the top athletes of the future? A large-scale study by researchers from the Vrije Universiteit Brussel SPLISS research group shows that there is no ready-made recipe. The road to the podium is non-linear and requires a holistic approach in which fun, health and the environment are central.

Hypoxia, a hallmark of the tumor microenvironment (TME), drives cancer progression through immune modulation, angiogenesis promotion, metabolic reprogramming, and uncontrolled cell proliferation. This review explores the diverse functions of hypoxia-inducible factor (HIF) signaling in cancer development and progression, providing a comprehensive overview of the molecular pathways. HIFs, particularly HIF-1α and HIF-2α, regulate several genes related to cancer hallmarks such as invasion, metabolic reprogramming, angiogenesis, and therapy resistance, thus mediating a significant portion of the hypoxic response. Oxygen-dependent hydroxylation of proline and asparagine residues in HIF-α subunits is a key regulator of their stability and transcriptional activity. Notably, this complex interaction is regulated by multiple signaling pathways, including the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK), phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. In cancer, HIF signaling affects several aspects of tumor cell biology that contribute to the cancerous characteristics, including angiogenesis induction through the upregulation of vascular endothelial growth factor (VEGF) expression, metabolic reprogramming through the enhancement of the Warburg effect, facilitation of cancer invasion and metastasis by driving epithelial-to-mesenchymal transition (EMT) and matrix remodeling patterns, and mediation of therapeutic resistance partly due to the effects on drug efflux pumps and DNA damage repair. Direct and indirect HIF inhibitors—including small molecules, peptidomimetics, antibodies, and proteolysis-targeting chimeras (PROTACs)—are under preclinical and clinical evaluation for their therapeutic efficacy. Preclinical and early clinical trials have demonstrated significant synergistic effects in inhibiting tumor development when HIF inhibition is combined with traditional therapies (chemotherapy or radiation) or immunotherapies, emphasizing major clinical implications and the potential for improving patient outcomes. Although challenges exist, particularly regarding drug resistance, further research to improve therapeutic efficacy and prolong survival for patients is warranted.

Customers' psychological engagement is essential to transforming the experience into results

Curtin University researchers have discovered some agricultural soils can naturally suppress one of Australia’s most damaging broadacre crop diseases.

Mushrooms, recognized for their culinary and medicinal applications, are emerging as promising autophagy modulators in cancer therapy. Autophagy is cellular degradation triggered by organelle damage, protein aggregation, metabolic disturbances, or nutrient scarcity. It contributes to the suppression of early tumor development and the promotion of cancer cell survival at advanced stages. This review systematically assesses the current evidence on the anticancer potential of mushrooms and their bioactive compounds, focusing on the ability of these mushrooms and their bioactive compounds to modulate autophagy. The review lists over 18 mushroom species (e.g., Ganoderma lucidum, Cordyceps, Phellinus) and 28 bioactive compounds (such as Ganoderic acid DM, Cordycepin, Hispidin) that affect autophagy, demonstrating efficacy against 15 cancer types, including colorectal, lung, breast, and liver cancers. Essential compounds modulate autophagy through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and Beclin-1 pathways, resulting in notable anticancer effects. G. lucidum extracts significantly reduced colorectal tumor growth by up to 60% in vivo. Additionally, Cordycepin induced autophagic cell death in lung cancer cells, with IC₅₀ values as low as 25 μmol/L. The findings highlight the potential of mushrooms as low-toxicity adjuvants to conventional therapies, providing advantages such as immune modulation and antioxidant activity. Mushrooms and their bioactive components present promising avenues for cancer therapy through the modulation of autophagy. The context-dependent effects of autophagy, along with the limited clinical evidence, present considerable challenges. Future clinical trials must focus on developing standardized extracts and personalized approaches to effectively translate this potential into clinical practice.