Search

Sai-Hong Ignatius Ou,1 Xiuning Le,2 Misako Nagasaka,1 Thanyanan Reungwetwattana,3 Myung-Ju Ahn,4 Darren WT Lim,5 Edgardo S Santos,6 Elaine Shum,7 Sally CM Lau,7 Jii Bum Lee,8 Antonio Calles,9 Fengying Wu,10 Gilberto Lopes,11 Virote Sriuranpong,12 Junko Tanizaki,13 Hidehito Horinouchi,14 Marina C Garassino,15 Sanjay Popat,16 Benjamin Besse,17 Rafael Rosell,18 Ross A Soo19 1University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange, CA, USA; 2University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 4Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 5Duke-NUS School of medicine, National Cancer Center Singapore, Republic of Singapore; 6Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA; 7NYU Langone Perlmutter Cancer Center, NY, NY, USA; 8Yonsei Cancer Center Yonsei University, Seoul, Republic of Korea; 9Department of Medicine, Division of Medical Oncology, Early Drug Development and Phase I Unit, Hospital General Universitario Gregorio Marañón, Madrid, 28007, Spain; 10Shanghai Chest hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 11Department of Medicine, Division of Medical Oncology, Sylvester Comprehensive Cancer Center at the University of Miami and the Miller School of Medicine, Miami, FL, 33136, USA; 12Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand; 13Department of Medicine, Kindai University School of Medicine, Osaka, Japan; 14Department of Thoracic Oncology, National Cancer Center Hospital Tokyo, Tokyo, Japan; 15Department of Medicine, Division of Medical Oncology-Hematology, University of Chicago Medicine, Chicago, IL, USA; 16Royal Marsden Hospital, London, Imperial College, London, UK; 17Gustave Roussy Cancer Campus, Villejuif, France; Paris-Saclay University, Orsay, France; 18Department of Hematology-Oncology, National University Cancer Institute, National University Hospital Singapore, Republic of Singapore; 19IOR, Quirón-Dexeus University Institute; ICO, Catalan Institute of Oncology; IGTP, Germans Trias i Pujol Research Institute, Barcelona, SpainCorrespondence: Sai-Hong Ignatius Ou, University of California School of Medicine, Department of Medicine, Division of Hematology-Oncology, Chao Family Comprehensive Cancer Center, 200 South Manchester Avenue, Suite 400, Orange, CA, 92868, USA, Tel +1 714-456-5153, Fax +1 714-456-2242, Email Siou@hs.uci.eduAbstract: The year 2024 is the 20th anniversary of the discovery of activating epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Since then, tremendous advances have been made in the treatment of NSCLC based on this discovery. Some of these studies have led to seismic changes in the concept of oncology research and spurred treatment advances beyond NSCLC, leading to a current true era of precision oncology for all solid tumors. We now routinely molecularly profile all tumor types and even plasma samples of patients with NSCLC for multiple actionable driver mutations, independent of patient clinical characteristics nor is profiling limited to the advanced incurable stage. We are increasingly monitoring treatment responses and detecting resistance to targeted therapy by using plasma genotyping. Furthermore, we are now profiling early-stage NSCLC for appropriate adjuvant targeted treatment leading to an eventual potential “cure” in early-stage EGFR+ NSCLC which have societal implication on implementing lung cancer screening in never-smokers as most EGFR+ NSCLC patients are never-smokers. All these advances were unfathomable in 2004 when the five papers that described “discoveries” of activating EGFR mutations (del19, L858R, exon 20 insertions, and “uncommon” mutations) were published. To commemorate this 20th anniversary, we assembled a global panel of thoracic medical oncology experts to select the top 20 papers (publications or congress presentation) from the 20 years since this seminal discovery with December 31, 2023 as the cutoff date for inclusion of papers to be voted on. Papers ranked 21 to 30 were considered “honorable mention” and also annotated. Our objective is that these 30 papers with their annotations about their impact and even all the ranked papers will serve as “syllabus” for the education of future thoracic oncology trainees. Finally, we mentioned potential practice-changing clinical trials to be reported. One of them, LAURA was published online on June 2, 2024 was not included in the list of papers to be voted on but will surely be highly ranked if this consensus survery is performed again on the 25th anniversay of the discovery EGFR mutations (i.e. top 25 papers on the 25 years since the discovery of activating EGFR mutations).Keywords: EGFR mutations, expert panel, top 20 papers, 20th anniversary, NSCLC

In the present work, the effect of Tb3+ doping in Cu ferrite is reported. Tb3+ doped Cu ferrite (CuTbxFe2-xO4) (x ​= ​0.0, 0.025, 0.05, 0.075, 0.1, 0.125, and 0.15) nanoparticles have been synthesized by Sol-Gel auto-combustion technique. The CuTbxFe2-xO4 ferrite crystallizes in spinel cubic structure. The presence of secondary phases is noticed. Characterization tools such as XRD, UV–visible, FTIR, and VSM are employed to investigate phase, structure, absorption bands, and magnetic properties. From XRD data the crystallite size is found to be in the range of 2.64–5.07nm. The FTIR pattern of synthesized ferrite describes the asymmetric stretching mode of spinel transition in CuFe2O4. The saturation magnetization of 22.96 emugm−1 is observed for CuFe2O4. From UV–visible DRS spectra the optical band gap energy of Tb3+ doped Cu ferrite samples is determined which shows decrease after doping. The antibacterial and antifungal activity of the synthesized nanoparticles were tested which shows good results.

Abstract FieldimageR.Extra is an advanced R package that enhances user experience and computational efficiency in analyzing orthomosaic images from agricultural field trials. Through the integration of modern GIS libraries like terra, stars, and sf, it surpasses traditional packages like raster and sp. The FieldimageR.Extra offers interactive visualization, vector feature creation, and spatial data editing within the R environment through the integration of mapview and mapedit packages. Notably, FieldimageR.Extra introduces new functions like fieldShape_render and fieldShape_edit, enabling flexible plot grid generation and editing capabilities. Comparative evaluations demonstrate the superior performance of FieldimageR.Extra in handling spatial data, crop and extract operations, and plot grid generation. With its comprehensive features, FieldimageR.Extra stands as a valuable addition to the FieldimageR R package, offering researchers efficient tools for unmanned aerial vehicle‐based orthomosaic image analysis in agricultural research. FIELDimageR.Extra is publicly available as a GitHub repository (https://github.com/filipematias23/FIELDimageR.Extra).

Hazel M O’Sullivan,1 Andrew Feber,2 Sanjay Popat1– 3 1Lung Unit, Royal Marsden NHS Foundation Trust, London, UK; 2The Institute of Cancer Research, London, UK; 3National Heart and Lung Institute, Imperial College London, London, UKCorrespondence: Sanjay Popat, The Lung Unit, The Royal Marsden Hospital, London, SW3 6JJ, United Kingdom, Tel +442073528171, Email sanjay.popat@rmh.nhs.ukAbstract: Circulating tumor DNA (ctDNA) analysis can identify patients with residual disease before it is clinically or radiologically evident. Minimal residual disease (MRD) is an advancing area in the management of radically treated solid tumors. Which MRD assay is optimum and when it should be used is still not defined. Whilst promising, the clinical utility of this technology to guide patient care is still investigational in non-small cell lung cancer (NSCLC) and has not entered routine care. Once technically and clinically optimized, MRD may be utilized to personalize adjuvant therapy, detect disease relapse earlier and improve cure rates. In this review, we discuss the current status of MRD monitoring in NSCLC by summarizing frequently used MRD assays and their associated evidence in NSCLC. We discuss the potential applications of these technologies and the challenge of demonstrating MRD clinical utility in trials.Keywords: MRD, ctDNA, NSCLC, adjuvant therapy, minimal residual disease, non-small cell lung cancer, circulating tumor DNA

Satoru Miura,1 Hyun Ae Jung,2 Shin Yup Lee,3 Seung Hyeun Lee,4 Min Ki Lee,5 Yong Chul Lee,6 Maximilian J Hochmair,7 Cheng-Ta Yang,8 Angela Märten,9 James Chih-Hsin Yang,10 Sanjay Popat11,12 1Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan; 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, South Korea; 5Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea; 6Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Medical School, Jeonju, South Korea; 7Department of Respiratory & Critical Care Medicine, Karl Landsteiner Institute of Lung Research & Pulmonary Oncology, Vienna, Austria; 8Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 9Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 10Department of Medical Oncology, National Taiwan University Cancer Center and Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 11Lung Unit, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; 12The Institute of Cancer Research, London, United KingdomCorrespondence: Sanjay Popat, Lung Unit, Royal Marsden National Health Service Foundation Trust, 203 Fulham Road, Chelsea, London, SW3 6JJ, United Kingdom, Tel +44-20-7808-2132, Email sanjay.popat@rmh.nhs.ukObjective: Two recent non-interventional trials, GioTag and UpSwinG, demonstrated encouraging time-to-treatment failure (TTF) and overall survival (OS) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) (Del19 or L858R) who received sequential afatinib/osimertinib, especially in Asians. Here, we have undertaken a combined analysis of Asian patients from both studies.Materials and Methods: Existing medical/electronic records were identified for consecutive EGFR-tyrosine kinase inhibitor (TKI)-naïve patients who received first-line afatinib/second-line osimertinib in “real-world” practice (all T790M-positive). Patients with active brain metastases were excluded. The primary objective was TTF. OS was a key secondary objective.Results: One hundred and sixty-eight patients were analyzed. Most patients were recruited from South Korea or Japan (52/21%). At the start of afatinib, median age (range) was 61.5 years (35– 88), 58% were female, Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0/1/≥ 2) was 29/62/9%, 17% had brain metastases, and EGFR mutation status (Del19/L858R) was 65/35%. At the start of osimertinib, ECOG PS (0/1/≥ 2) was 22/61/17% and 14% had brain metastases. Median TTF and OS were 30.0 months (95% CI: 24.5– 32.5) and 45.2 months (95% CI: 41.7– 71.1), respectively. Median OS was 63.5 months in patients with a Del19 mutation. Median OS in patients with brain metastases or ECOG PS ≥ 2 was 26.4 and 33.1 months, respectively.Conclusion: Sequential afatinib/osimertinib showed encouraging activity in Asian patients with EGFR mutation-positive NSCLC and T790M-mediated acquired resistance, especially those with Del19-positive disease. Activity was observed across “real-world” patients including those with poor ECOG PS and/or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib.Graphical Abstract: Keywords: EGFR, afatinib, osimertinib, sequential, T790M

BackgroundAnti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction.Patients and methodsWe conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation.ResultsWe studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2).Conclusions: ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Cancer remains a major health concern and second leading cause of mortality worldwide. The highest cancer-related mortalities are observed in low and middle-income countries (LMIC) due to unaffordable cost of medicines and lack of safe and effective chemotherapy. Therefore, the key goal of the present research was to develop affordable, safe, efficacious and stable nanoemulsion (NE) system co-loaded with Tadalafil (TDF) and Ketoconazole (KTZ) for repurposing against hepatic cancer. The batch number 1 of SNEDDS was selected as optimized batch based on dispersion time, viscosity and stability. The NE displayed particle size of 41±5 nm (PDI: 0.189±0.064) and Zeta potential of -27.1 mV. The NE exhibited controlled in-vitro release of both TDF (52.37 ± 3.41%) and (KTZ 52.31 ± 3.88%) in PBS pH 6.8 after 24 h. Moreover, the in-vitro hemolysis study showed moderate hemolytic activity of NE towards blood cells. In addition, the in-vitro cytotoxicity study revealed more cytotoxicity of NE than plain TDF and KTZ against HepG2 cell line after 48 h of incubation. Moreover, the HepG2 cellular uptake of TDF and KTZ was found to be substantially higher from NE when compared to the plain TDF and KTZ. Furthermore, NE was found to be stable for more than 6 months with no phase separation and creaming. Stable, safe, effective and affordable NE was developed which might be used as an alternative strategy in the treatment of hepatic cancer and its similar anticancer effect against other cancers need to be validated. Further, TDF and KTZ combination would a potentials approach over approved chemotherapy against hepatic cancer.

Role of excipients in designing diverse dosage forms has been highly acclaimed and needs no introduction. These are integral components of pharmaceutical formulations and determine the structure of a dosage form and its function in drug delivery. In many instances, combating the numerous diseases using active therapeutic agents is ultimately challenging task owing to marred solubility and permeability, multidrug resistance, poor pharmacokinetics and associated toxicities, and stability of the drug itself or delivery system. In that context, excipients modulate product aspects such as stability, biopharmaceutical profile, and patient compatibility. D-ɑ-tocopheryl polyethylene glycol succinate (TPGS) is a FDA approved safe and biocompatible adjuvant and acknowledged in pharmaceutical industries for their notable properties namely solubilizer, absorption and permeation enhancer, emulsifier and stabilizer, etc. Moreover, it performs ample bio-functions like anticancer agent, P-gp and cytochrome P450 inhibitor that eventually assist in escalating the therapeutic performance of the drugs. Furthermore, use of TPGS in nanomedicines is reported to be fruitful in improving anticancer potential and pharmacokinetic properties of relevant molecules. By 2025, the international nanomedicine market is projected to reach USD 350.8 billion. Hence, the TPGS-based nanomedicines can emerge as a promising approach for different diseases and can occupy the market in few years. The present review is focused on the pharmaceutical properties of TPGS with the major emphasis on TPGS-based nanomedicines and drug delivery via different routes. Furthermore, the biological and biomedical properties of TPGS are briefed. Thus, use of TPGS in the development of pharmaceutical formulation can be propitious and thus anticipated to offer better therapeutic performance of the cargo.

Abstract Background Podophyllotoxin (PPT) is a naturally occurring compound obtained from the roots of Podophyllum species, indicated for a variety of malignant tumors such as breast, lung, and liver tumors. This toxic polyphenol (PPT) exhibited significant activity against P-glycoprotein (P-gp) mediated multidrug-resistant (MDR) cancer cells. However, extremely poor water solubility, a narrow therapeutic window, and high toxicity have greatly restricted the clinical uses of PPT. Therefore, the present research was aimed to synthesize the water-soluble ester prodrug of PPT with polyacrylic acid (PAA), a water-soluble polymer by Steglich esterification reaction, and to screen it for assay, solubility, in vitro hemolysis, in vitro release, and in vitro anticancer activity. Results The Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy results revealed the successful synthesis of podophyllotoxin-polyacrylic acid conjugate (PPC). The assay and saturation solubility of the prodrug is found to be 64.01 ± 4.5% and 1.39 ± 0.05 mg/mL (PPT equivalent) respectively. The PPC showed CMC (critical micelle concentration) of 0.430 mg/mL in distilled water at room temperature. The PPC micelles showed a mean particle size of 215 ± 11 nm with polydispersity index (PDI) of 0.193 ± 0.006. Further, the transmission electron microscope (TEM) results confirmed the self-assembling character of PPC into micelles. The PPC caused significantly less hemolysis (18.6 ± 2.9%) than plain PPT solution. Also, it demonstrated significantly (p < 0.01) higher in vitro cytotoxicity against both sensitive as well as resistance human breast cancer cells (MCF-7 and MDA MB-231) after 48 h of treatment. Conclusion The obtained study results clearly revealed the notable in vitro anticancer activity of PPT following its esterification with PAA. However, further in vivo studies are needed to ascertain its efficacy against a variety of cancers.

COVID-19 pandemic is taking a dangerous turn due to unavailability of approved and effective vaccines and therapy. Currently available diagnostic techniques are time-consuming, expensive, and maybe impacted by the mutations produced in the virus. Therefore, investigation of novel, rapid, and economic diagnosis techniques, prophylactic vaccines and targeted efficacious drug delivery systems as treatment strategy is imperative. Carbohydrates are essential biomolecules which also act as markers in the realization of immune systems. Moreover, they exhibit antiviral, antimicrobial, and antifungal properties. Carbohydrate-based vaccines and therapeutics including stimuli sensitive systems can be developed successfully and used effectively to fight COVID-19. Thus, carbohydrate-based diagnostic, prophylactic and therapeutic alternatives could be promising to defeat COVID-19 propitiously. Morphology of SARS-CoV-2 and its relevance in devising combat strategies has been discussed. Carbohydrate-based approaches for tackling infectious diseases and their importance in the design of various diagnostic and treatment modalities have been reviewed.

Abstract Background Methotrexate (MTX), a folate anti-metabolite, has been used widely in the treatment of plenty of malignancies. However, the clinical use is limited because of its poor water solubility (BCS class II drug), nonspecific distribution, drug resistance, short circulation half-life, and toxicity. The objective of the present research was to synthesize the ester prodrug of MTX with d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and characterize for in vitro anticancer efficacy. Results The FTIR and NMR results revealed the successful synthesis of the prodrug. The assay and saturation solubility of the prodrug is found to be 23 ± 2.5% and 6.7 ± 1.3 mg/mL (MTX equivalent) respectively. The CMC of the prodrug in distilled water at room temperature is found to be 36.9 ± 2.6 μg/mL. The prepared prodrug micelles showed a mean particle size of 166 ± 10 nm (PDI, 0.325 ± 0.09). Further, the TEM results confirmed the self-assembling character of the prodrug into micelles with a nearly spherical shape. The prodrug caused the significantly (p < 0.01) less hemolysis (16.8 ± 1.5%) when compared to plain MTX solution and significantly higher (p < 0.01) in vitro cytotoxicity, cell cycle arresting, and apoptosis against human breast cancer cells (MCF-7 and MDA-MB-231). Conclusion Our study results revealed the remarkable in vitro anticancer activity of MTX following its esterification with TPGS. However, further, in vivo studies are needed to prove its efficacy against different cancers.

The objective of this article is to graphically illustrate to the students the physical phenomenon of motion of charged particle under the action of simultaneous electric and magnetic fields by simulating particle motion on a computer. Differential equations of motions are solved analytically and path of particle in three-dimensional space are obtained using interactive spreadsheet. Spreadsheets can be setup to solve numerical solutions of complex systems. This will make the concept, which so far is left to the abstract imagination come alive for the student, and initiate a deeper understanding of particle motion.