Selpercatinib mitigates cancer cachexia independent of anti-tumor activity in the HT1080 tumor model.

Anorexia is a major cause of cancer cachexia and is induced by growth differentiation factor-15 (GDF15), which activates the rearranged during transfection (RET) protein tyrosine kinase in the hindbrain through GDF family receptor α-like (GFRAL), raising the possibility of targeting RET for cancer cachexia treatment. RET-altered cancer patients treated with RET-selective kinase inhibitors gain weight, however, it is unclear whether this results from tumor regression that improves the overall health of patients. Thus, the potential of using a RET inhibitor to address cancer cachexia remains unknown.

Tissue-Agnostic Targeting of Neurotrophic Tyrosine Receptor Kinase Fusions: Current Approvals and Future Directions.

fusions are oncogenic drivers for multiple tumor types. Therefore, the development of selective tropomyosin receptor kinase (TRK) inhibitors, including larotrectinib and entrectinib, has been transformative in the context of clinical management, given the high rates of responses to these drugs, including intracranial responses in patients with brain metastases. Given their promising activity in pan-cancer cohorts, larotrectinib and entrectinib received U.

Predictive Significance of Combined Plasmatic Detection of BRAF Mutations and S100B Tumor Marker in Early-Stage Malignant Melanoma.

Background: Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma.

Methods: Eighty patients were enrolled in the study.

Unveiling the impact of circulating tumor cells: Two decades of discovery and clinical advancements in solid tumors.

Circulating tumor cells (CTCs) enumeration and molecular profiling hold promise in revolutionizing the management of solid tumors. Their understanding has evolved significantly over the past two decades, encompassing pivotal biological discoveries and clinical studies across various malignancies. While for some tumor types, such as breast, prostate, and colorectal cancer, CTCs are ready to enter clinical practice, for others, additional research is required.

Effects of Emotional Olfactory Stimuli on Modulating Angry Driving Based on an EEG Connectivity Study.

Effectively regulating anger driving has become critical in ensuring road safety. The existing research lacks a feasible exploration of anger-driving regulation. This paper delves into the effect and neural mechanisms of emotional olfactory stimuli (EOS) on regulating anger driving based on EEG.

Knowledge, attitude, and practice of Egyptian medical students towards healthcare workers' recommended vaccines: a nationwide cross-sectional survey.

Background: Vaccination of healthcare workers (HCWs) is pivotal in decreasing the incidence of contagious infections in hospital settings. In this study, we assessed the knowledge, attitude, and practice regarding HCWs' recommended vaccines among medical students and interns in Egypt.

Methods: A multicenter, cross-sectional study was conducted using a structured, pilot-tested, and self-administered questionnaire among Egyptian medical students and interns.

Appraising critical success factors in sustainable housing projects: A comparative study of PPP modalities in Saudi Arabia.

This study examines the critical success factors (CSFs) crucial for the effective deployment of public-private partnership (PPP) models in sustainable housing projects in the Kingdom of Saudi Arabia (KSA), underpinning the nation's Vision 2030. Through a robust methodology that incorporates a profound literature review, structured interviews, and a survey involving key stakeholders, the study prioritizes fourteen significant CSFs integral to PPP efficacy. Employing Analytical Hierarchy Process analysis, key outcomes underscore the paramount importance of technical aspects with an emphasis on sustainability, tailoring risk-sharing and allocation to encompass green technologies and eco-friendly practices, and economic stability in the light of long-term environmental sustainability in fostering successful sustainable housing projects.

Evaluation of insurance policies in the Saudi Arabian construction contracts.

The construction sector is more complicated and prone to risk than many other industries due to the size of the projects and the financial capital involved. Arranging insurance is the prudent course of action for risk management in the construction sector. There is a lack of clarity in insurance policies for public construction projects in the Kingdom of Saudi Arabia (KSA), which poses additional risks to all involved contracting parties.

The evolving landscape of tissue-agnostic therapies in precision oncology.

Tumor-agnostic therapies represent a paradigm shift in oncology by altering the traditional means of characterizing tumors based on their origin or location. Instead, they zero in on specific genetic anomalies responsible for fueling malignant growth. The watershed moment for tumor-agnostic therapies arrived in 2017, with the US Food and Drug Administration's historic approval of pembrolizumab, an immune checkpoint inhibitor.

Adaptive Darwinian off-target resistance mechanisms to selective RET inhibition in RET driven cancer.

Patients treated with RET protein tyrosine kinase inhibitors (TKIs) selpercatinib or pralsetinib develop RET TKI resistance by secondary RET mutations or alterative oncogenes, of which alterative oncogenes pose a greater challenge for disease management because of multiple potential mechanisms and the unclear tolerability of drug combinations. A patient with metastatic medullary thyroid carcinoma (MTC) harboring a RET activation loop D898_E901del mutation was treated with selpercatinib. Molecular alterations were monitored with tissue biopsies and cfDNA during the treatment.

Tissue-Agnostic Cancer Therapy Approvals.

Tumor-agnostic, or histology-agnostic, cancer therapy marks a groundbreaking evolution in the realm of precision oncology. In stark contrast to conventional cancer treatments that categorize malignancies based on their tissue of origin (eg, breast, lung, renal cell, etc), tumor-agnostic therapies transcend histologic boundaries, honing in on the genetic and molecular attributes of tumors, regardless of their location. This article offers a comprehensive review of the current landscape of tissue-agnostic cancer therapies and provides clinical insights to empower surgical oncologists with a deeper understanding of these innovative therapeutic approaches.

Colonoscopy screening for colorectal cancer in Egypt: a nationwide cross-sectional study.

Background: Current guidelines advocate for colorectal cancer (CRC) screening in adults who are at risk by using direct visualization methods such as colonoscopy. However, in Egypt, there is a paucity of data regarding the current practice of colonoscopy screening. Moreover, more information is needed about the knowledge and attitudes of potential participants regarding the procedure and possible barriers that can limit their participation.

Impact of tissue-agnostic approvals on management of primary brain tumors.

Novel tissue-agnostic therapeutics targeting driver mutations in tumor cells have been recently approved by FDA, driven by basket trials that have demonstrated their efficacy and safety across diverse tumor histology. However, the relative rarity of primary brain tumors (PBTs) has limited their representation in early trials of tissue-agnostic medications. Thus, consensus continues to evolve regarding utility of tissue-agnostic medications in routine practice for PBTs, a diverse group of neoplasms characterized by limited treatment options and unfavorable prognoses.

Synthesis of sEMG Signals for Hand Gestures Using a 1DDCGAN.

The emergence of modern prosthetics controlled by bio-signals has been facilitated by AI and microchip technology innovations. AI algorithms are trained using sEMG produced by muscles during contractions. The data acquisition procedure may result in discomfort and fatigue, particularly for amputees.

Strategies for mitigating adverse events related to selective RET inhibitors in patients with RET-altered cancers.

The US Food and Drug Administration (FDA) approval of the selective RET inhibitors selpercatinib and pralsetinib has led to a paradigm change in the treatment of RET-altered lung and thyroid cancers through a higher response rate and a more tolerable safety and toxicity profile than multi-kinase inhibitors. Recently, selpercatinib has received a tissue-agnostic FDA approval for all RET-fusion-positive cancers, and pralsetinib has shown pan-cancer activity as well. Given the anticipated increase in the use of both drugs across multiple tumor types, it is crucial to recognize the possible side effects and approaches for their optimal management in order to maximize the clinical benefit for treated patients.

In-Depth Analysis of Incidence and Survival of Lacrimal Gland Malignancies in the United States of America from 1995 to 2018.

Purpose: To investigate lacrimal gland malignancies' incidence and survival rates in the USA between 1995 and 2018.

Methods: Incidence and survival data from the North American Association of Central Cancer Registries of lacrimal gland malignancies between 1996 and 2018 were extracted and analyzed.

Results: This study analyzed data pertaining to 3620 patients (females 56.

Selinexor: Changing the paradigm in patients with TP53 wild-type endometrial cancer?

Recurrent endometrial cancer (EC) remains a therapeutic challenge despite advancements in personalized medicine. SIENDO trial showed the potential clinical benefit of selinexor in patients with TP53 wild-type advanced/recurrent EC. The quest for novel therapeutic avenues and approaches continues as researchers seek a glimmer of hope in an area of uncertainty.

ALK fusions in the pan-cancer setting: another tumor-agnostic target?

Anaplastic lymphoma kinase (ALK) alterations (activating mutations, amplifications, and fusions/rearrangements) occur in ~3.3% of cancers. ALK fusions/rearrangements are discerned in >50% of inflammatory myofibroblastic tumors (IMTs) and anaplastic large cell lymphomas (ALCLs), but only in ~0.

Activity of pazopanib in translocation-associated bone sarcoma.

Pazopanib is a multi-kinase inhibitor that is currently approved for treatment of advanced renal cell carcinoma and chemotherapy-refractory soft tissue sarcoma. In this case report, we discuss the case of a patient with a fusion positive bone sarcoma who had exceptional tumor control through using pazopanib and surgery for an overall duration exceeding 5 years. We also review the literature on translocation-associated sarcomas and use of pazopanib in bone sarcomas.

Multi-disciplinary management of recurrent gastrointestinal stromal tumor harboring KIT exon 11 mutation with the switch-control kinase inhibitor ripretinib and surgery.

Ripretinib is a tyrosine kinase inhibitor that was approved by the United States FDA in 2020 for treatment of advanced gastrointestinal stromal tumor (GIST) in patients who received prior treatment with three or more tyrosine kinase inhibitors. In this case report, we show the durable clinical benefit achieved in a patient with GIST by using ripretinib and repeated timely surgical resection of limited disease progression. The total time on ripretinib was 43 months which is longer than the current reported data from ripretinib clinical trials.

Long-Term Survival in Patients with Cancers: Surveillance, epidemiology and end results-based analysis.

Objectives: This study aimed to explore real-world data on the long-term survival of cancer patients using historical records from the Surveillance, Epidemiology, and End Results (SEER) Programme. Long-term survival is an important endpoint in the management of different malignancies. It is rarely assessed due to the unfeasibility of follow-up for a long duration of time.

The Landscape of Alterations from 1407 Ultra-Rare Sarcomas from the AACR GENIE Database: Clinical Implications.

Purpose: Ultra-rare sarcomas (URS) comprise a group of orphan diseases with an incidence of ≤1/1,000,000 people per year. We aimed to assess clinically actionable genomic alterations in URS.

Experimental Design: Data were extracted from the GENIE database using cBioPortal.

Pearls and pitfalls of ChatGPT in medical oncology.

Recently, ChatGPT has drawn attention to the potential uses of artificial intelligence (AI) in academia. Here, we discuss how ChatGPT can be of value to medicine and medical oncology and the potential pitfalls that may be encountered.