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Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response.

Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on m

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… Dormant tumor cells exhibit a reversible cell cycle arrest in G0-G1 phase, in which they remain viable but do not proliferate. Thus, quiescent cancer cells represent a clinical challenge since they are commonly chemo-resistant. … Specifically, osteoblast-derived TGF-β2 activates TGF-βRIII signaling in PCa cells with a subsequent phosphorylation of p38MAPK and interruption of the cell-cycle in G1-phase through the increase of the cell cycle inhibitor p27 ( 54 ). …

Targeting phosphatidylinositol-3-kinase pathway for the treatment of Philadelphia-negative myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPN) are a diverse group of chronic hematological disorders that involve unregulated clonal proliferation of white blood cells. Sevearl of them are associated with mutations in receptor tyrosine kinases or cytokine receptor associated tyrosine kinases rendering them independent of cytokine-mediated regulation. Classically they have been broadly divided into BCR-ABL1 fusion + ve (Ph + ve) or -ve (Ph-ve) MPNs. Identification of BCR-ABL1 tyrosine kinase as a driver of chronic myeloid leukemia (CML) and successful application of small molecule inhibitors of the tyrosi

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… BEZ235, a dual specificity inhibitor of the PI3K/ mTOR pathway developed by Novartis inhibited the proliferation of growth factor independent, clonal proerythroblastic murine cells as well as human mast cell line carrying the D816V mutation with cells being arrested in G1 phase [ 95 , 96 ]. …

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for th

Radioprotectors & mitigators in radiation therapy: Harnessing diverse pathways for optimizing clinical outcomes.

Radioprotectors are agents that protect normal tissues from the harmful effects of radiation during cancer treatment. Combining these protective agents with advanced radiotherapy techniques such as stereotactic body radiotherapy (SBRT) and proton therapy offers a promising strategy to enhance therapeutic efficacy while minimizing normal tissue toxicity. However, despite extensive research and the identification of numerous potential radioprotectors, only a few have made it into clinical practice. It is primarily because the transition from laboratory research to clinical application faces sign

Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

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Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects.

The overall approach to the treatment of multiple myeloma (MM) has undergone several changes during the past decade. and proteasome inhibitors (PIs) including bortezomib, carfilzomib, and ixazomib have considerably improved the outcomes in affected patients. The first-in-class selective PI bortezomib has been initially approved for the refractory forms of the disease but has now become, in combination with other drugs, the backbone of the frontline therapy for newly diagnosed MM patients, as well as in the maintenance therapy and relapsed/refractory setting. Despite being among the most widely

The Potential of Mushroom Extracts to Improve Chemotherapy Efficacy in Cancer Cells: A Systematic Review.

Chemoresistance is a challenge in cancer treatment, limiting the effectiveness of chemotherapy. Mushroom extracts have shown potential as treatments for cancer therapies, offering a possible solution to overcome chemoresistance. This systematic review aimed to explore the role of mushroom extracts in enhancing chemotherapy and reversing chemoresistance in cancer cells. We searched the PubMed, Web of Science and Scopus databases, following the PRISMA guidelines, and registered on PROSPERO. The extracts acted by inhibiting the proliferation of cancer cells, as well as enhancing the effect of che

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… After NK cell activation, a significant increase in NK CD16+CD56+ cell populations was noted, which were activated and showed 74.09% cytotoxic effects against human colon cancer Caco-2 cells, stopping them in the G0/G1 phase and leading to apoptosis. …

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidan

Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.

Therapeutic resistance remains a major obstacle to durable cancer control, with functional reprogramming of the DNA damage response (DDR) network playing a central role. The poly(ADP-ribose) polymerase (PARP) family, particularly PARP1 and PARP2, is crucial for maintaining genomic integrity. By exploiting synthetic lethality, PARP inhibitors (PARPi) selectively target tumors with homologous recombination deficiency (HRD) and are integral to precision therapy in ovarian, breast, and prostate cancers. However, over 40% of patients with BRCA1/2 alterations develop resistance, and patient eligibil

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… During G1 phase, the recruitment of 53BP1 and RIF1 to DSBs suppresses BRCA1 loading and end resection, thereby favoring NHEJ [ 114 , 125 , 127 ]. … Further analysis revealed that this combination induced a significant G0/G1 phase arrest (78.4% vs. 58.3% in the control group) and upregulated apoptotic proteins such as Bax (1.8-fold) and Caspase-3 (5.3-fold), indicating that this combination induces both intrinsic and extrinsic apoptotic pathways …

The potential of mesenchymal stem cells in the management of radiation enteropathy.

Although radiotherapy is effective in managing abdominal and pelvic malignant tumors, radiation enteropathy is still unavoidable. This disease severely affects the quality of life of cancer patients due to some refractory lesions, such as intestinal ischemia, mucositis, ulcer, necrosis or even perforation. Current drugs or prevailing therapies are committed to alleviating the symptoms induced by above lesions. But the efficacies achieved by these interventions are still not satisfactory, because the milieus for tissue regeneration are not distinctly improved. In recent years, regenerative ther

Trial watch: Monoclonal antibodies in cancer therapy.

During the past 20 years, dozens-if not hundreds-of monoclonal antibodies have been developed and characterized for their capacity to mediate antineoplastic effects, either as they activate/enhance tumor-specific immune responses, either as they interrupt cancer cell-intrinsic signal transduction cascades, either as they specifically delivery toxins to malignant cells or as they block the tumor-stroma interaction. Such an intense research effort has lead to the approval by FDA of no less than 14 distinct molecules for use in humans affected by hematological or solid malignancies. In the inaugu

LAP2α drives breast tumorigenesis by mitigating replication stress.

Replication protein A (RPA) plays a vital role in replication stress response, with RPA-coated single-stranded DNA (ssDNA) acting as a critical platform for the coordination of the genome surveillance machinery. In previous studies, we reported that the lamin-associated protein LAP2α interacts physically with RPA, aiding its localization to damaged chromatin for genome protection. However, the significance of the LAP2α-mediated RPA deposition in tumor progression remains unclear. Here, we reveal that LAP2α promotes breast tumorigenesis by counteracting replication stress-induced DNA damage. Fu

Monoclonal Antibodies: Leading Actors in the Relapsed/Refractory Multiple Myeloma Treatment.

Multiple myeloma is a complex hematologic malignancy, and despite a survival improvement related to the growing number of available therapeutic options since 2000s, it remains an incurable disease with most patients experiencing relapse. However, therapeutic options for this disease are constantly evolving and immunotherapy is becoming the mainstay of the therapeutic armamentarium of Multiple Myeloma (MM), starting with monoclonal antibodies (MoAbs) as elotuzumab, daratumumab and isatuximab. Elotuzumab, the first in class targeting SLAMF7, in combination with lenalidomide and dexamethasone and

Summary for clinicians: ERS guidelines on pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease caused by accumulation of surfactant in the alveoli, leading to debilitating respiratory symptoms and impaired gas exchange. The recent European Respiratory Society guidelines provide evidence-based recommendations for its diagnosis and management. Autoimmune PAP (aPAP) is the most common form, driven by granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies. Recommended diagnostic tools include bronchoalveolar lavage and quantitative GM-CSF antibody testing. Whole lung lavage and inhaled GM-CSF are first-line treatm

Current Landscape of Genome-Wide Association Studies in Acute Myeloid Leukemia: A Review.

Acute myeloid leukemia (AML) is a clonal hematopoietic disease that arises from chromosomal and genetic aberrations in myeloid precursor cells. AML is one of the most common types of acute leukemia in adults; however, it is relatively rare overall, comprising about 1% of all cancers. In the last decade or so, numerous genome-wide association studies (GWAS) have been conducted to screen between hundreds of thousands and millions of variants across many human genomes to discover genetic polymorphisms associated with a particular disease or phenotype. In oncology, GWAS has been performed in almos

Новое применение XPO1 для лечения миэлофиброза.

Myelofibrosis (MF) — новообразование, характеризующееся конституционными симптомами, прогрессивными цитопентиями и селеногамели. В основе патобологии MF лежит активация мутации на пути JAK/STAT и регулирование цитокинового костного мозга. Хотя многие ингибиторы JAK в настоящее время официально утверждены и обеспечивают значительное улучшение симптомов, эти агенты не имеют курса на изменение потенциала. Кроме того, результаты являются неудовлетворительными для пациентов, которые не справляются с ингибиторами JAK, что подчеркивает необходимость применения новых методов лечения, основанных на исп

Penfluridol inhibits melanoma growth and metastasis through enhancing von Hippel‒Lindau tumor suppressor-mediated cancerous inhibitor of protein phosphatase 2A (CIP2A) degradation.

Melanoma's high metastatic potential, especially to the brain, poses significant challenges to patient survival. The blood‒brain barrier (BBB) is a major obstacle to the effective treatment of melanoma brain metastases. We screened antipsychotic drugs capable of crossing the BBB and identified penfluridol (PF) as the most active candidate. PF reduced melanoma cell viability and induced apoptosis. In animal models, PF effectively inhibited melanoma growth and metastasis to the lung and brain. Using immunoprecipitation combined with high-resolution mass spectrometry, and other techniques such as

Митохондриальная передача метаболических перепрограмм и лекарственная устойчивость в метастазе костей: механизмы и терапевтические стратегии.

Кость это one из наиболее распространенных участков удаленного метастаза в твердых опухолях, в частности рак груди, рак простаты и рак легких. Метатические повреждения костей часто свидетельствуют о стойком сопротивлении многосистемной терапии, включая химиотерапию, целевую терапию, эндокринную терапию и ингибиторы иммунных контрольно-пропускных пунктов (ИПК). Накопляющиеся данные свидетельствуют о том, что метаболическая перепрограммирование в пределах костной микроокружающей среды способствует этому сопротивлению, однако механизмы в верхнем течении по-прежнему недостаточно понятны. В качеств

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… CDK4/6 inhibitors, by arresting the cell cycle at G1 phase, may extend the time window during which transfer can occur ( 117 ). …

Interplay between stress and cancer-A focus on inflammation.

Stress is an integral part of life. While acute responses to stress are generally regarded as beneficial in dealing with immediate threats, chronic exposure to threatening stimuli exerts deleterious effects and can be either a contributing or an aggravating factor for many chronic diseases including cancer. Chronic psychological stress has been identified as a significant factor contributing to the development and progression of cancer, but the mechanisms that link chronic stress to cancer remain incompletely understood. Psychological stressors initiate multiple physiological responses that re