Oncogene-addicted solid tumors and microbiome-lung cancer as a main character: a narrative review.

Background and Objective: Lung cancer stands as the main cause of cancer-related deaths worldwide. With the advent of immunotherapy and the discovery of targetable oncogenic driver genes, although prognosis has changed in the last few years, survival rates remain dismal for most patients. This emphasizes the urgent need for new strategies that could enhance treatment in precision medicine. The role of the microbiota in carcinogenesis constitutes an evolving landscape of which little is known. It has been suggested these microorganisms may influence in responses, resistance, and adverse effects to cancer treatments, particularly to immune checkpoint blockers. However, evidence on the impact of microbiota composition in oncogene-addicted tumors is lacking. This review aims to provide an overview of the relationship between microbiota, daily habits, the immune system, and oncogene-addicted tumors, focusing on lung cancer. Methods: A PubMed and Google Scholar search from 2013 to 2024 was conducted. Relevant articles were reviewed in order to guide our research and generate hypothesis of clinical applicability. Key Content and Findings: Microbiota is recognized to participate in immune reprogramming, fostering inflammatory, immunosuppressive, or anti-tumor responses. Therefore, identifying the microbiota that impact response to treatment and modulating its composition by interventions such as dietary modifications, probiotics or antibiotics, could potentially yield better outcomes for cancer patients. Additionally, targeted therapies that modulate molecular signaling pathways may impact both immunity and microbiota. Understanding this intricate interplay could unveil new therapeutic strategies. Conclusions: By comprehending how microbiota may influence efficacy of targeted therapies, even though current evidence is scarce, we may generate interesting hypotheses that could improve clinical practice.

New promises and challenges in the treatment of advanced non-small-cell lung cancer.

Targeted therapies and immunotherapies have radically improved treatment for advanced non-small-cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting oncogenic driver mutations continue to evolve over multiple generations to enhance effectiveness and tackle drug resistance. Immune checkpoint inhibitors remain integral for the treatment of NSCLCs that do not have specific actionable genetic mutations. Antibody-drug conjugates and bispecific antibodies are being integrated into treatment guidelines, and emerging therapies include T-cell engagers, cellular therapies, cancer vaccines, and external devices. Despite these advances, challenges remain in identifying predictive biomarkers to individually tailor treatments, abrogate resistance, reduce costs, and ensure optimal cancer treatment accessibility.

Calls to action on lung cancer management and research.

Lung cancer, the leading cause of cancer-related deaths globally, remains a pressing health issue despite significant medical advances. The New York Lung Cancer Foundation brought together experts from academia, the pharmaceutical and biotech industries as well as organizational leaders and patient advocates, to thoroughly examine the current state of lung cancer diagnosis, treatment, and research. The goal was to identify areas where our understanding is incomplete and to develop collaborative public health and scientific strategies to generate better patient outcomes, as highlighted in our "Calls to Action." The consortium prioritized 8 different calls to action. These include (1) develop strategies to cure more patients with early-stage lung cancer, (2) investigate carcinogenesis leading to lung cancers in patients without a history of smoking, (3) harness precision medicine for disease interception and prevention, (4) implement solutions to deliver prevention measures and effective therapies to individuals in under-resourced countries, (5) facilitate collaborations with industry to collect and share data and samples, (6) create and maintain open access to big data repositories, (7) develop new immunotherapeutic agents for lung cancer treatment and prevention, and (8) invest in research in both the academic and community settings. These calls to action provide guidance to representatives from academia, the pharmaceutical and biotech industries, organizational and regulatory leaders, and patient advocates to guide ongoing and planned initiatives.

Rediscovering immunohistochemistry in lung cancer.

Several observations indicate that protein expression analysis by immunohistochemistry (IHC) remains relevant in individuals with non-small-cell lung cancer (NSCLC) when considering targeted therapy, as an early step in diagnosis and for therapy selection. Since the advent of next-generation sequencing (NGS), the role of IHC in testing for NSCLC biomarkers has been forgotten or ignored. We discuss how protein-level investigations maintain a critical role in defining sensitivity to lung cancer therapies in oncogene- and non-oncogene-addicted cases and in patients eligible for immunotherapy, suggesting that IHC testing should be reconsidered in clinical practice. We also argue how a panel of IHC tests should be considered complementary to NGS and other genomic assays. This is relevant to current clinical diagnostic practice but with potential future roles to optimize the selection of patients for innovative therapies. At the same time, strict validation of antibodies, assays, scoring systems, and intra- and interobserver reproducibility is needed.

[Adverse effects of new breast cancer therapies : when to react ?] / Effets indésirables des nouvelles thérapies du cancer du sein : quand faut-il réagir ?

In last years, the therapeutic arsenal against breast cancer increased considerably with the arrival of signaling pathway inhibitors, immunotherapy, PARP inhibitors, tyrosine kinase inhibitors and antibody-drug conjugates. Consequently, the range of potential adverse events has also widened and differs from the usual chemotherapies and endocrine therapies. Depending on the administered therapy, the same symptoms can be harmless and treated symptomatically or the warning sign of a potential serious complication requiring a rapid action. We therefore discuss in this article the therapeutic role and some typical adverse events of these new therapies.

Ces dernières années, l'arsenal thérapeutique contre le cancer du sein s'est passablement enrichi avec les inhibiteurs des voies de signalisation, l'immunothérapie, les inhibiteurs de PARP (polyADP-ribose polymérase), les inhibiteurs de tyrosine kinase et les chimiothérapies immunoconjuguées. De ce fait, la gamme d'effets indésirables potentiels s'est également élargie et diffère des habituelles chimiothérapies et hormonothérapies. En fonction de la substance administrée, les mêmes symptômes peuvent être anodins et traités symptomatiquement, ou alors être le signe d'alerte d'une potentielle complication sévère et nécessiter une réaction rapide. Nous discutons dans cet article du rôle thérapeutique et des quelques effets indésirables typiques de ces nouvelles thérapies.

[2021 Oncology update]. / Oncologie.

Despite COVID-19 pandemic, which is still deeply affecting world economy and global health, medical oncology specialists keep pursuing their effort for the identification of new therapeutic options to improve patients' life expectancy and quality of life. 2021 confirms the immunotherapy efficacy, alone or in combination with other modalities, across several indications. This year, we are summarizing the new approaches in the following sectors: lung, breast, melanoma, gynecological, digestive, urological and ENT areas.

En dépit de la pandémie de Covid-19 qui continue à grandement impacter l'économie mondiale et la santé, l'oncologie médicale poursuit sa quête d'identification de nouvelles options thérapeutiques ayant pour buts la prolongation de l'espérance de vie et l'amélioration de la qualité de vie de ses patients, en nombre croissant. L'année 2021 confirme également l'efficacité de l'immunothérapie, seule ou en combinaison à d'autres modalités, dans de nombreuses indications. Cette année, nous vous résumons les nouvelles approches dans les domaines suivants: poumon, sein, mélanome, sphères gynécologique, digestive, urologique et ORL.

Slowness Predicts Mortality: A Comparative Analysis of Walking Speed and Moberg Picking-Up Tests.

OBJECTIVES: Slow walking speed (WS) is predictive of mortality but may be difficult to measure, which compromises the assessment of frailty, based on Fried et al's phenotype. The timed Moberg picking-up test (MPUT), developed to evaluate hand's function, was found moderately but significantly correlated with WS. We compared the relationship between slowness, assessed by MPUT and WS tests, and mortality. DESIGN: Observational (prospective cohort study). SETTING AND PARTICIPANTS: 4731 community-dwelling adults included in 2004, 2009, or 2014 in the ongoing Lausanne cohort 65+ (Lc65+) were assessed at the age of 66-71 years. METHOD: Mortality was compared for individuals above and below percentile 80 of MPUT, and respectively WS performance time, according to the Fried criterion. Multivariable analysis using Cox's regression models were adjusted for age, sex, height and grip strength. The predictive capability of MPUT and WS was assessed in adjusted models using Harrell C. RESULTS: Slowness in MPUT and in WS test was associated with mortality at 4, 9, and 14 years (P < .001). Survival curves showed lower survival rates in the highest percentile for both tests (P < .001), regardless of the follow-up period. Cox models indicated a higher risk of death at 4 years [adjusted hazard ratio (95% confidence interval): MPUT, 2.1 (1.5-3.0); WS, 2.2 (1.5-3.1)], 9 years [MPUT 1.7 (1.3-2.3); WS 2.0 (1.5-2.6)] and 14 years [MPUT 1.8 (1.4-2.3); WS 1.8 (1.4-2.4)] for participants above the 80th percentile (all P < .001). The 2 tests had similar predictive capability (Harrell C: MPUT, between 61% and 68%; WS, between 62% and 69%). CONCLUSIONS AND IMPLICATIONS: Poor performance in MPUT is associated with increased mortality at the short and long term among community-dwelling older adults. This alternative to WS in the assessment of slowness has similar predictive capability for mortality and avoids biased estimates because of nonrandom exclusion of individuals unable to complete WS.