Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (NSCLC) Treatment: Quo Vadis?

Lung cancer has been established as the second most common cancer worldwide (most common cancer in men and second most common cancer in women) and as the leading cause of cancer morbidity among neoplasms [...].

The Impact of the COVID-19 Pandemic on Elite Swimmers and Water Polo Players: Lessons for the Future.

BACKGROUND: The COVID-19 pandemic has disrupted global daily life, including the world of elite athletes. This paper examines the multifaceted impact the COVID-19 pandemic had on elite swimmers and water polo athletes, specifically their mental health, their concerns over the virus, their intentions of getting vaccinated, and sleep disturbances that they may have faced. METHODS: We conducted a cross-sectional study on elite swimmers and water polo players, using an anonymous questionnaire. RESULTS: A total of 200 elite athletes participated. The majority of the participants reported a negative impact on their mental health, screened positive for insomnia (n = 107 (53.5%), with females (n = 101; 57.7%), swimmers (n = 100, 66.7%), and university students (n = 71, 71.7%) being more vulnerable (p < 0.001). Concerns about contracting the disease especially during important training or tournament periods and potential career disruption also affected their psychological well-being. While the majority (75%) had the intention of getting vaccinated, an alarming percentage was yet uncertain over its decision. CONCLUSIONS: This study highlights the significant psychological distress faced by elite aquatic athletes during the pandemic. It emphasizes the difficulties faced by elite swimmers and water polo athletes and determines not only the importance of addressing the vaccination intentions of athletes, but also how critical it is to confront the challenges they face both for their personal health and for the restoration of world sports to their pre-pandemic state. More large-scale studies are required to inform policies targeted at minimizing disruption to the athletes' career, provision of information on preventive measures and vaccination, and improvement in psychological well-being in case of similar major public health issues in the future. Additionally, this study calls for further research to explore the unique challenges faced by aquatic athletes, such as those related to their training environments and fear of contagion, to better support them in future public health crises.

Hungry for fat: Metabolic crosstalk with lipid-rich CAFs fuels pancreatic cancer.

Some cancers prefer to metabolize lipids for their growth and metastasis. In a recent Cancer Cell study, Niu et al. revealed that SET domain containing 2, histone lysine methyltransferase (SETD2)-deficient pancreatic cancer cells induce the differentiation of lipid-laden cancer-associated fibroblasts (CAFs), which, in turn, transport lipids to promote tumor growth.

Up to the Herculean Task of Tackling Cancer Therapy Resistance.

Cancer therapy resistance still poses the biggest hurdle to cancer treatment [...].

RAF and MEK Inhibitors in Non-Small Cell Lung Cancer.

Lung cancer, despite recent advancements in survival rates, represents a significant global health burden. Non-small cell lung cancer (NSCLC), the most prevalent type, is driven largely by activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and receptor tyrosine kinases (RTKs), and less in v-RAF murine sarcoma viral oncogene homolog B (BRAF) and mitogen-activated protein-kinase kinase (MEK), all key components of the RTK-RAS-mitogen-activated protein kinase (MAPK) pathway. Learning from melanoma, the identification of BRAFV600E substitution in NSCLC provided the rationale for the investigation of RAF and MEK inhibition as a therapeutic strategy. The regulatory approval of two RAF-MEK inhibitor combinations, dabrafenib-trametinib, in 2017, and encorafenib-binimetinib, in 2023, signifies a breakthrough for the management of BRAFV600E-mutant NSCLC patients. However, the almost universal emergence of acquired resistance limits their clinical benefit. New RAF and MEK inhibitors, with distinct biochemical characteristics, are in preclinical and clinical development. In this review, we aim to provide valuable insights into the current state of RAF and MEK inhibition in the management of NSCLC, fostering a deeper understanding of the potential impact on patient outcomes.

Anthocyanins in Non-Small Cell Lung Cancer (NSCLC) Treatment and Prevention.

An ever-growing volume of data supports the important role of dietary interventions in cancer prevention and the beneficial effects of plant secondary metabolites in solid tumor therapeutics [...].

Malolactone strikes: K-Ras-G12D's Achilles' heel.

In a recent study in Nature Chemical Biology, Zheng et al. exploiting strain release by malolactone-based electrophiles designed a first-in-class covalent inhibitor that targets the elusive aspartate of the Kirsten rat sarcoma viral oncogene homolog (K-Ras)-G12D variant, which is highly prevalent in pancreatic cancer. The compound drastically inhibited oncogenic signaling and tumor growth in preclinical K-Ras-G12D-mutant pancreatic cancer models, expanding treatment potential beyond K-Ras-G12C-targeted therapies.

Mechanotransduction Circuits in Human Pathobiology.

It is widely acknowledged that mechanical forces exerted throughout the human body are critical for cellular and tissue homeostasis [...].

SOX17: escape route from immune destruction in early CRC.

In a recent report in Nature, Goto et al. reveal a novel immune-evasion mechanism adopted by early colorectal cancer (CRC) cells that is based on the transcription factor sex determining region Y (SRY)-box transcription factor 17 (SOX17). Leveraging colorectal adenoma and cancer models to perform comprehensive transcriptomic/chromatin analyses, this work shows that SOX17 generates immune-silent leucine-rich repeat-containing G protein-coupled receptor 5- (LGR5-) tumor cells, which suppress interferon gamma (IFNγ) signaling and promote immune escape.

YAP/TAZ-TEAD signalling axis: A new therapeutic target in malignant pleural mesothelioma.

The Hippo signalling pathway, a highly conserved signalling cassette, regulates organ size by controlling cell growth, apoptosis and stem cell self-renewal. The tumourigenic potential of this pathway is largely attributed to the activity of YAP/TAZ, which activate the TEAD1-4 transcription factors, leading to the expression of genes involved in cell proliferation and suppression of cell death. Aberrant regulation of the YAP/TAZ-TEAD signalling axis is commonly observed in malignant pleural mesothelioma (MPM), an insidious neoplasm of the pleural tissue that lines the chest cavity and covers the lungs with poor prognosis. Given the limited effectiveness of current treatments, targeting the YAP/TAZ-TEAD signalling cascade has emerged as a promising therapeutic strategy in MPM. Several inhibitors of the YAP/TAZ-TEAD signalling axis are presently undergoing clinical development, with the goal of advancing them to clinical use in the near future.

P53 and Rb Aberrations in Small Cell Lung Cancer (SCLC): From Molecular Mechanisms to Therapeutic Modulation.

The genes coding for the tumor suppressors p53 and retinoblastoma (Rb) are inactivated in the vast majority of small cell lung cancer (SCLC) tumors. Data support the notion that these two deleterious genetic events represent the initial steps in the development of SCLC, making them essential for a lung epithelial cell to progress toward the acquisition of a malignant phenotype. With the loss of TP53 and RB1, their broad tumor suppressive functions are eliminated and a normal cell is able to proliferate indefinitely, escape entering into cellular senescence, and evade death, no matter the damage it has experienced. Within this setting, lung epithelial cells accumulate further oncogenic mutations and are well on their way to becoming SCLC cells. Understanding the molecular mechanisms of these genetic lesions and their effects within lung epithelial cells is of paramount importance, in order to tackle this aggressive and deadly lung cancer. The present review summarizes the current knowledge on p53 and Rb aberrations, their biological significance, and their prospective therapeutic potential, highlighting completed and ongoing clinical trials with agents that target downstream pathways.

mTOR Signaling: Recent Progress.

In the intricate landscape of human biology, the mechanistic target of rapamycin (mTOR) emerges as a key regulator, orchestrating a vast array of processes in health and disease [...].

Many faces, many places: delving deeper into CAF heterogeneity in NSCLC.

In a recent study published in Cancer Cell, Cords et al. employed multiplexed imaging mass cytometry to analyze cancer-associated fibroblast (CAF) heterogeneity in 1070 NSCLC patients. This work defined good and poor prognostic CAF phenotypes, the latter associated with metastasis and chemoresistance, as well as revealed that CAF spatial location correlates with immune cell infiltration and clinical outcome.

Targeting the TGF-ß Signaling Axis in Metastatic Colorectal Cancer: Where Do We Stand?

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide [...].

Angiotensin-Converting Enzyme 2 (ACE2) Signaling in Pulmonary Arterial Hypertension: Underpinning Mechanisms and Potential Targeting Strategies.

Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling processes that lead to right-ventricular heart failure and, ultimately, death. Although our understanding of its pathophysiology has advanced and several treatment modalities are currently available for the management of PAH patients, none are curative and the prognosis remains poor. Therefore, further research is required to decipher the molecular mechanisms associated with PAH. Angiotensin-converting enzyme 2 (ACE2) plays an important role through its vasoprotective functions in cardiopulmonary homeostasis, and accumulating preclinical and clinical evidence shows that the upregulation of the ACE2/Angiotensin-(1-7)/MAS1 proto-oncogene, G protein-coupled receptor (Mas 1 receptor) signaling axis is implicated in the pathophysiology of PAH. Herein, we highlight the molecular mechanisms of ACE2 signaling in PAH and discuss its potential as a therapeutic target.