Exploring the Potential of Antibody-Drug Conjugates in Targeting Non-small Cell Lung Cancer Biomarkers.

Antibody-drug conjugates (ADCs), combining the cytotoxicity of the drug payload with the specificity of monoclonal antibodies, are one of the rapidly evolving classes of anti-cancer agents. These agents have been successfully incorporated into the treatment paradigm of many malignancies, including non-small cell lung cancer (NSCLC). The NSCLC is the most prevalent subtype of lung cancer, having a considerable burden on the cancer-related mortality and morbidity rates globally. Several ADC molecules are currently approved by the Food and Drug Administration (FDA) to be used in patients with NSCLC. However, the successful management of NSCLC patients using these agents was met with several challenges, including the development of resistance and toxicities. These shortcomings resulted in the exploration of novel therapeutic targets that can be targeted by the ADCs. This review aims to explore the recently identified ADC targets along with their oncologic mechanisms. The ADC molecules targeting these biomarkers are further discussed along with the evidence from clinical trials.

Ethnic differences in hepatocellular carcinoma prevalence and therapeutic outcomes.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The incidence of HCC is affected by genetic and non-genetic factors. Genetically, mutations in the genes, tumor protein P53 (TP53), catenin beta 1 (CTNNB1), AT-rich interaction domain 1A (ARIC1A), cyclin dependent kinase inhibitor 2A (CDKN2A), mannose 6-phosphate (M6P), smooth muscle action against decapentaplegic (SMAD2), retinoblastoma gene (RB1), cyclin D, antigen presenting cells (APC), AXIN1, and E-cadherin, have been shown to contribute to the occurrence of HCC. Non-genetic factors, including alcohol consumption, exposure to aflatoxin, age, gender, presence of hepatitis B (HBV), hepatitis C (HCV), and non-alcoholic fatty liver disease (NAFLD), increase the risk of HCC. RECENT FINDINGS: The severity of the disease and its occurrence vary based on geographical location. Furthermore, men and minorities have been shown to be disproportionately affected by HCC, compared with women and non-minorities. Ethnicity has been reported to significantly affect tumorigenesis and clinical outcomes in patients diagnosed with HCC. Generally, differences in gene expression and/or the presence of comorbid medical diseases affect or influence the progression of HCC. Non-Caucasian HCC patients are significantly more likely to have poorer survival outcomes, compared to their Caucasian counterparts. Finally, there are a number of factors that contribute to the success rate of treatments for HCC. CONCLUSION: Assessment and treatment of HCC must be consistent using evidence-based guidelines and standardized outcomes, as well as international clinical practice guidelines for global consensus. Standardizing the assessment approach and method will enable comparison and improvement of liver cancer research through collaboration between researchers, healthcare providers, and advocacy groups. In this review, we will focus on discussing epidemiological factors that result in deviations and changes in treatment approaches for HCC.

Contracting triple-negative breast cancer with immunotherapeutic armamentarium: recent advances and clinical prospects.

Triple negative breast cancer (TNBC) portraying deficient expression of estrogen receptor (ER), progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) is known to be the most aggressive subtype associated with poor prognosis and interventional strategies limited to chemotherapy and breast conserving surgery. Some TNBC incidences have also been reported with positive circ-HER2 expression thus rendering circ-HER2 a potential immunotherapy target to direct drug development. Resistance and recurrence reported with traditional approaches has led us towards the application of immunotherapeutic interventions owing to their anti-tumor efficacy. This review provides an elaborative insight on potential molecular biomarkers to be targeted by immunotherapy. Additionally, clinical trials proposing the application of immunotherapy in neoadjuvant, adjuvant and metastatic TNBC setting have also been included. The gathered evidence indicates a positive application of immunotherapy in TNBC with therapeutic limitation available only owing to the possibility of adverse events which can be dealt considering risk-to-benefit ratio. Furthermore, potential targets to aim for therapeutic vaccines along with evidence from clinical trials have also been mentioned.

Unveiling the antibody-drug conjugates portfolio in battling Triple-negative breast cancer: Therapeutic trends and Future horizon.

Triple-negative breast cancer (TNBC) showcases a labyrinthine network exhibiting deficient expression of Estrogen receptor (ER), Progesterone receptor (PR), and Human-epidermal growth factor receptor-2 (HER2). This restricts the conventional chemotherapeutic, hormonal, and few targeted regimens in showing efficient anti-tumor response. Antibody-drug conjugates (ADCs) are target-specific conjugates comprising a monoclonal antibody attached to the desired cytotoxic payload with the support of a stable linker. They are designated as one of the encouraging sets of targeted therapies that have unveiled affirmative outcomes owing to increased specificity in targeting the undetectable or deficiently expressed targets. Another virtue of ADCs lending superiority to this approach is the presence of inherent bystander effect which has a detrimental influence on the tumor microenvironment (TME) devoid of antigen expression. In the current scenario, FDA-approved Sacituzumab govitecan is widely being utilized to mitigate TNBC while many other ADCs are being studied in clinical trials. Additionally, a focus has been set on revelation of application of Trastuzumab deruxtecan in HER2-low metastatic breast cancer which widens the current therapeutic horizon dealing with such carcinomas. After making an effort towards sketching ADCs profile, we conclude that this novel approach deserves to be investigated through future campaigns owing to its remarkable bystander effect, ability to precisely recognize the antigen and spare the naïve cells from detrimental toxicity. Exploration of the remarkable potential of Sacituzumab govitecan in multiple indications including TNBC portrays the prominence of ADCs and prompts the bright future of this therapeutic approach. In this review, we present the basic foundation of ADCs alongside summarizing the building blocks of several ADCs used in TNBC. Furthermore, by shedding light on the therapeutic regimens and concomitant effects of various ADCs derived from the supportive backbone of clinical trials, we have attempted to convene several segments of ADCs and portray their potentialities time ahead.

mRNA-Based Vaccines and Therapeutics for COVID-19 and Future Pandemics.

An unheard mobilization of resources to find SARS-CoV-2 vaccines and therapies has been sparked by the COVID-19 pandemic. Two years ago, COVID-19's launch propelled mRNA-based technologies into the public eye. Knowledge gained from mRNA technology used to combat COVID-19 is assisting in the creation of treatments and vaccines to treat existing illnesses and may avert pandemics in the future. Exploiting the capacity of mRNA to create therapeutic proteins to impede or treat a variety of illnesses, including cancer, is the main goal of the quickly developing, highly multidisciplinary field of biomedicine. In this review, we explore the potential of mRNA as a vaccine and therapeutic using current research findings.

A large-volume sputum dry storage and transportation device for molecular and culture-based diagnosis of tuberculosis.

Technologies for preservation of specimens in the absence of cold chains are essential for optimum utilization of existing laboratory services in the developing world. We present a prototype called specimen transportation tube (SPECTRA-tube) for the collection, exposure-free drying, ambient transportation, and liquid state recovery of large-volume (>1 mL) specimens. Specimens introduced into the SPECTRA-tube are dried in glass fiber membranes, which are critical for efficient liquid-state sample recovery by rehydration and centrifugation. SPECTRA-tube is demonstrated for the dry storage of sputum for tuberculosis detection. Mycobacterium smegmatis (Msm)-spiked mock sputum dried in a native Standard 17 glass fiber was stable for molecular testing after 10 day storage at 45 °C and for culture testing after 10- and 5-day storage at 37 °C and 45 °C, respectively. Compatibility with human sputum storage was demonstrated by dry storing 1.2 mL Mycobacterium bovis-spiked human sputum in a SPECTRA-tube for 5 days at room temperature. We have thus demonstrated the first workflow for dry storage of sputum followed by molecular and culture testing. Compared to existing specimen dry storage technologies, SPECTRA-tube significantly increases the volume of liquid specimens that can be transported in the dry state and enables the recovery of the entire sample in the liquid state, rendering it compatible with conventional downstream analysis methods.

Anti-Androgenic Therapies Targeting the Luminal Androgen Receptor of a Typical Triple-Negative Breast Cancer.

Triple-negative tumors are progressively delineating their existence over the extended spectrum of breast cancers, marked by intricate molecular heterogeneity, a low overall survival rate, and an unexplored therapeutic approach. Although the basal subtype transcends the group and contributes approximately 80% to triple-negative breast cancer (TNBC) cases, the exceptionally appearing mesenchymal and luminal androgen receptor (LAR) subtypes portray an unfathomable clinical course. LAR with a distinct generic profile frequently metastasizes to regional lymph nodes and bones. This subtype is minimally affected by chemotherapy and shows the lowest pathologic complete response. The androgen receptor is the only sex steroid receptor that plays a cardinal role in the progression of breast cancers and is typically overexpressed in LAR. The partial AR antagonist bicalutamide and the next-generation AR inhibitor enzalutamide are being assessed in standard protocols for the mitigation of TNBC. There arises an inevitable need to probe into the strategies that could neutralize these androgen receptors and alleviate the trajectory of concerning cancer. This paper thus focuses on reviewing literature that provides insights into the anti-androgenic elements against LAR typical TNBC that could pave the way for clinical advancements in this dynamic sphere of oncology.

Paper Stacks for Uniform Rehydration of Dried Reagents in Paper Microfluidic Devices.

Spatially uniform reconstitution of dried reagents is critical to the function of paper microfluidic devices. Advancing fluid fronts in paper microfluidic devices drive (convect) and concentrate rehydrated reagents to the edges, causing steep chemical gradients and imperfect mixing. This largely unsolved problem in paper microfluidics is exacerbated by increasing device dimensions. In this article, we demonstrate that mixing of dried reagents with a rehydrating fluid in paper microfluidics may be significantly enhanced by stacking paper layers having different wicking rates. Compared to single-layer paper membranes, stacking reduced the "non-reactive area", i.e. area in which the reconstituted reagents did not interact with the rehydrating fluid, by as much as 97% in large (8 cm × 2 cm) paper membranes. A paper stack was designed to collect ~0.9 ml liquid sample and uniformly mix it with dried reagents. Applications of this technology are demonstrated in two areas: (i) collection and dry storage of sputum samples for tuberculosis testing, and (ii) salivary glucose detection using an enzymatic assay and colorimetric readout. Maximizing the interaction of liquids with dried reagents is central to enhancing the performance of all paper microfluidic devices; this technique is therefore likely to find important applications in paper microfluidics.

Morphology of functioning trabeculectomy blebs using anterior segment optical coherence tomography.

PURPOSE: To image trabeculectomy blebs using anterior segment optical coherence tomography (AS-OCT), and to correlate the bleb morphologic features at one month postoperatively with bleb function at six months. MATERIALS AND METHODS: This prospective, observational study included 56 eyes undergoing trabeculectomy with MMC, followed up for minimum of six months. Postoperatively, bleb imaging was done using AS-OCT at one and six month. Bleb morphology was assessed for bleb wall reflectivity, bleb pattern in multiform reflectivity, visibility of drainage route and presence of hyper-reflectivity area. Bleb function was considered successful if IOP was <18 mmHg without medication at six month. Bleb morphology one month postoperatively was correlated with bleb function at six months. RESULTS: At six months successful bleb function was noted in 44 (81.5%) eyes. Morphology of bleb at one month showed uniform bleb wall reflectivity in 6 eyes (11%) and multiform wall reflectivity in 48 eyes (89%). In eyes with multiform wall reflectivity, microcysts with multiple layers was seen in 26 eyes (48%), microcysts with subconjunctival separation in 12 eyes (22%) and only microcyst in 10 eyes (19%). When bleb features at one month were correlated with the bleb function at six months, logistic regression analysis revealed that blebs with multiform reflectivity with multiple internal layers with microcysts were associated with higher chances of success (P < 0.001). CONCLUSION: AS-OCT demonstrated early bleb morphological features that may be used to predict the functioning of a bleb. Multiform bleb wall reflectivity with a pattern of multiple internal layers and microcysts was associated with increased chances of success of a bleb.