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Unlocking the potential of tumor-targeting peptides in precision oncology.

Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy, which is often plagued by poor selectivity, off-target effects, and drug resistance. Among the various targeting agents in development, peptides stand out for their unique advantages, including minimal immunogenicity, high tissue penetration, and ease of modification. Their small size, specificity, and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively. Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery, improvi

The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.

Immunity to solid tumors is associated with the hallmarks of cancer-associated inflammation and the ability of immune mechanisms to limit tumor progression. Application of expanded tumor-infiltrating lymphocyte adoptive T cell therapy (TIL ACT) in clinical trials is now practiced at many sites around the world. Prior to immune checkpoint blockade (ICB), an approximate 50% objective response rate was consistently observed across multiple institutions for patients with melanoma. This now-approved strategy approaches 35% in recent studies from the USA and 49% with more highly selected patients in

Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth.

Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following forma

The multiple roles of interferon regulatory factor family in health and disease.

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of v

Essential Concepts for the Management of Metastatic Spine Disease: What the Surgeon Should Know and Practice.

Study designLiterature review.ObjectiveTo provide an overview of the recent advances in spinal oncology, emphasizing the key role of the surgeon in the treatment of patients with spinal metastatic tumors.MethodsLiterature review.ResultsTherapeutic advances led to longer survival times among cancer patients, placing significant emphasis on durable local control, optimization of quality of life, and daily function for patients with spinal metastatic tumors. Recent integration of modern diagnostic tools, precision oncologic treatment, and widespread use of new technologies has transformed the tre

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… Single-dose radiotherapy disables tumor cell homologous recombination via ischemia/reperfusion injury [published online January 14, 2018]. J Clin Invest. doi:10.1172/JCI97631 52. Katsoulakis E, Laufer I, Bilsky M, Agaram NP, Lovelock M, Yamada Y. …

The Critical Role of Hypoxic Microenvironment and Epigenetic Deregulation in Esophageal Cancer Radioresistance.

Esophageal cancer (EC) is the seventh most common cancer worldwide and the sixth leading cause of death, according to Globocan 2018. Despite efforts made for therapeutic advances, EC remains highly lethal, portending a five-year overall survival of just 15-20%. Hence, the discovery of new molecular targets that might improve therapeutic efficacy is urgently needed. Due to high proliferative rates and also the limited oxygen and nutrient diffusion in tumors, the development of hypoxic regions and consequent activation of hypoxia-inducible factors (HIFs) are a common characteristic of solid tumo

Erythropoiesis-Stimulating Agents in the Management of Anemia in Chronic Kidney Disease or Cancer: A Historical Perspective.

Anemia is common in patients with cancer or with chronic kidney disease (CKD). Although the introduction of erythropoiesis-stimulating agents (ESAs) has transformed the management of anemia, their use has been complicated by a number of factors including frequent guideline updates, safety concerns and, in the United States, a Risk Evaluation and Mitigation Strategy (REMS) program, which aimed to ensure that the benefits of ESAs outweigh the risks. Many previous concerns around ESA use in cancer and CKD have been addressed by the reassuring results of post-approval studies, and biosimilar ESAs

Selected Abstracts from the 13th Annual Meeting of the Clinical Immunology Society: 2022 Annual Meeting: Immune Deficiency and Dysregulation North American Conference

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Glioblastoma Treatment: State-of-the-Art and Future Perspectives.

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Recently, bevacizumab has been added to the treatment arsenal for the recurrent scenario. Nevertheless, patients with glioblastoma still have a poor prognosis. Therefore, many efforts are being made in different clinical research areas to find a new alternative to improve ove

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

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Bispecific antibodies in multiple myeloma treatment: A journey in progress.

The incorporation of novel agents and monoclonal antibody-based therapies into the treatment of multiple myeloma (MM) has significantly improved long-term patient survival. However, the disease is still largely incurable, with high-risk patients suffering shorter survival times, partly due to weakened immune systems. Bispecific molecules, including bispecific antibodies (BisAbs) and bispecific T-cell engagers (BiTEs), encourage immune cells to lyse MM cells by simultaneously binding antigens on MM cells and immune effector cells, bringing those cells into close proximity. BisAbs that target B-

Chimeric Antigen Receptor T-Cell Therapy in Metastatic Castrate-Resistant Prostate Cancer.

Prostate cancer is the most commonly diagnosed solid-organ cancer amongst males worldwide. Metastatic castrate-resistant prostate cancer (mCRPC) is a rapidly fatal end-sequelae of prostate cancer. Therapeutic options for men with mCRPC are limited and are not curative in nature. The recent development of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionised the treatment of treatment-resistant haematological malignancies, and several studies are underway investigating the utility of this technology in the treatment of solid tumours. In this review, we evaluate the current treatme

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… This was following the improved objective response rates demonstrated in individuals harbouring homologous recombination repair (HRR) defects such as BRCA1/BRCA2/ATM mutations [ 27 , 28 ]. …

Genomic profiling enables personalized strategies to overcome drug resistance in multiple myeloma.

Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. It is a complex and heterogeneous disease that primarily affects older adults and is associated with significant morbidity and mortality. Despite advances in treatment, including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, MM remains largely incurable, with most patients experiencing relapse and disease progression. The disease’s biological complexity is driven by a multitude of genetic and molecular alterations, which contr

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… . | Overexpression of PARP1 contributing to resistance to PARP inhibitors; increased activity of homologous recombination and non-homologous end-joining pathways. …

Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies.

Antibody-drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies' targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they

Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications.

Bone metastases represent a critical complication in oncology, frequently indicating advanced malignancy and substantially reducing patient quality of life. This review provides a comprehensive analysis of the complex interactions between tumor cells and the bone microenvironment, emphasizing the relevance of the "seed and soil" hypothesis, the RANK/RANKL/OPG signaling axis, and Wnt signaling pathways that collectively drive metastatic progression. The molecular and cellular mechanisms underlying the formation of osteolytic and osteoblastic lesions are examined in detail, with a particular foc

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… For instance, in patients with metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair gene alterations, including those with bone metastases, olaparib dramatically increased radiographic progression-free survival and overall survival, according to the PROfound trial … Regarding BRCA-mutated prostate cancer with bone metastases in patients with mCRPC who had homologous recombination repair gene changes, the phase 3 PROfound trial compared olaparib to enzalutamide or abiraterone. …

Реконструкция петли антикодона и форма D-стима приводят к конкретному распознаванию ANN-декодирования tRNA для модификации t6A.

N6-threonylcarbamoyladenosine (t6A) — универсальная трансфертная модификация RNA (tRNA), необходимая для перевода. Модификация устанавливается в положение 37 ANN-декодирование tRNAs (N is A, U, G или C) путем переноса треонилкарбамойла из промежуточного пути, катализированного в бактериях комплексом ЦаБД. Несмотря на строгое требование в отношении 36-UAA-38 Последовательность в субстрате tRNS, структурная основа этой специфичности остается неясной. Мы определили крио-эм-структуры "Термотога маритима Т6А" синтазы, связанные с немодифицированной и изначально модифицированной ТRNA с модификацией

Структурный анализ процесса сбора света с помощью антенн, содержащих родопсины в морской архееи Асгарда.

Акватические бактериальные редопсиновые протонные насосы собирают световую энергию для фотогетертрофного роста и, как известно, содержат гидроксилированные каротеи, расширяющие волны используемого света, но они не характеризуются морской археей. Здесь, комбинируя морскую хромофорную экстракт с очищенными архейскими родопсинами, выявленными в морских метагеномах, мы показываем передачу легкой энергии из различных гидроксилоидных каротеоидных в геймдаллархаэ (HeimdallRs) из некультурных морских планктонных членов «Candidatus Cariarachaeceae» (Candidatus Asgardarchaeota). Эти светообрабатывающие

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… K. pelagium’ MAGs were inconsistent with the HeimdallR1/R2 divide (Fig. 2b ), which might be a result of binning artefacts or ongoing intraspecific homologous recombination. Extended Data Fig. 4 Global distribution of “ Ca . …

Prospects and Challenges of Lung Cancer Vaccines.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have modestly improved patient survival, their overall efficacy remains limited, and the prognosis is generally poor. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. Nevertheless, the immunosuppressive tumor microenvironment, tumor heterogeneity, and immune escape mechanisms significantly restrict the clinical benefit, which falls short of expectations. Within this contex