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Microbiota-derived metabolites as modulators of cancer immunotherapy response.

The microbiome is a key regulator of host homeostasis and immune activity, in part through the production of metabolites. These microbiota-derived metabolites can modulate both the innate and adaptive immune system, as well as directly target tumour cells, thereby regulating anti-tumour immunity and response to immunotherapy. Here, we describe the current mechanistic knowledge on how these metabolites exert their effects and outline the methodologies used to detect and assess these metabolites. Finally, we summarize microbiota-targeted therapies capable of improving microbial functionality to

FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial.

Fc receptor-homolog 5 (FcRH5) is a membrane protein that is ubiquitously expressed on myeloma cells. Cevostamab is a first-in-class, FcRH5×CD3 bispecific antibody. GO39775 is a phase 1 dose-escalation and dose-expansion study evaluating fixed-duration cevostamab in relapsed or refractory multiple myeloma. Cevostamab was initiated with step-up dosing and continued at the target dose (TD) once every 3 weeks for 17 cycles (~12 months) unless disease progression or unacceptable toxicity occurred. Primary objectives were to evaluate safety, including determination of the maximum tolerated dose (MTD

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… Data on cevostamab retreatment were also not included in the current analysis and will be reported elsewhere. …

Surviving Cancer, Lacking Support: The Hidden Burden of Modern Radiation Oncology in the Treatment of Oligometastatic Disease.

The management of oligometastatic disease has undergone a significant paradigm shift over the past two decades. Once considered uniformly incurable, selected patients with metastatic disease can now achieve prolonged progression-free survival, durable disease control, and, in carefully selected cases, long-term remission or cure through metastasis-directed therapies. Advances in stereotactic ablative radiotherapy (SABR), surgery, systemic therapies, and the emerging concept of Curative Oligometastatic Radiotherapy (CORT) have challenged the traditional distinction between curative and palliati

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… Techniques Although SABR currently represents the best-supported local treatment modality for oligometastatic disease, several other radiotherapy technologies could potentially be applied to further improve the therapeutic ratio by increasing treatment precision, reducing toxicity, or enabling safer retreatment …

Recent advances in tumor immunotherapy based on NK cells.

Immunotherapy has emerged as the established fourth pillar of cancer treatment following surgery, radiotherapy, and chemotherapy, representing a cutting-edge research domain in translational medicine and clinical oncology. Natural killer (NK) cells, a type of innate cytotoxic lymphocyte, possess unique antitumor properties that are independent of major histocompatibility complex (MHC) restrictions, making them promising candidates for "off-the-shelf" therapeutic products. NK cells can eliminate tumor cells through various mechanisms. Genetic engineering of NK cells can enhance their activation

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… Retreatment Needs | Effective with single infusion, but re-preparation is required for recurrence. | May require multiple infusions (e.g., once every 2 weeks); long-term costs need to be evaluated alongside efficacy. …

T-клеток, перенаправляющих терапию на рецидив миеломы.

В последние годы использование иммуномодуляционных препаратов, протеиозных ингибиторов и CD38, направленных против моноклонных антител, привело к значительному улучшению общих результатов пациентов с множественной миеломой. Несмотря на эти достижения, рецидивы остаются обычным явлением, и до недавнего времени прогнозы таких пациентов охранялись. Одобрение T-клеток химерика антигенного рецептора (CAR) и Т-комплексов (TCE) значительно повысило выживаемость этих пациентов с тройной и пента-классовой рефракторной болезнью. В настоящем документе рассматриваются клинические результаты, связанные с э

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… Salvage therapies including retreatment with BCMA-directed approaches after BCMA CAR-T relapses for multiple myeloma. Blood Adv. 2024;8:2207–16. 10.1182/bloodadvances.2023012066. 52. Costa LJ, et al. …

Exosomes and organ-specific metastasis.

The transmission of information between tumor cells and other cell types in the tumor microenvironment plays an important role in tumor metastasis and is critically modulated by exosomes and other mediators. Tumor-derived exosomes can promote epithelial-mesenchymal transition, angiogenesis, immune escape, formation of the pre-metastatic microenvironment, and transmission of drug-resistant molecules, thereby promoting tumor growth, invasion, and metastasis. Integrins are important regulatory molecules on exosomes that can locate metastatic cells at the initial stage of metastasis and show good

Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies.

Neuromyelitis optica (NMO) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by acute optic neuritis (ON) and transverse myelitis (TM). NMO is caused by a pathogenic serum IgG antibody against the water channel aquoporin 4 (AQP4) in the majority of patients. AQP4-antibody (AQP4-ab) presence is highly specific, and differentiates NMO from multiple sclerosis. It binds to AQP4 channels on astrocytes, triggering activation of the classical complement cascade, causing granulocyte, eosinophil, and lymphocyte infiltration, culminating in injury first to as

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… Maintenance: 1 g with retreatment at 2 weeks every 6 mo. or one infusion of 375 mg/m 2 every 6 mo. | Chimeric monoclonal antibody (IgG1) against human CD20. …

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

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… However, patients harboring the L1198F mutation, which confers resistance to lorlatinib, have reported re-sensitivity to crizotinib. 30 This result indicates that retreatment under molecular guidance should be considered as a clinically meaningful approach for ALK -positive NSCLC. … Meanwhile, it has also been reported that some mutations are sensitive to the second-generation inhibitors, such as T315A to nilotinib, E255K/V and Y253H to dasatinib and bosutinib, and patients harboring such mutations can be retreated with these drugs. …

Chemoprevention in Skin Cancer: What Advice?

The incidence of melanoma and non-melanoma skin cancers (NMSCs) is increasing worldwide. While NMSCs are more common, melanoma remains the most challenging because of its higher aggressiveness. Although the use of sunscreens is key in high-risk populations, it provides limited protection, which highlights the need for alternative solutions. In this review, we discuss current evidence on chemopreventive therapies, as well as their efficacy and adverse events, including immunocompetent and immunosuppressed patients. Acitretin, nicotinamide, 5-fluorouracil, and photodynamic therapy have shown ove

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… Rechallenge and retreatment with topical imiquimod 5% in transplant recipients: A multicenter experience on actinic keratoses and basal cell carcinomas JEADV Clin. Pract. 2024 3 1447 1453 10.1002/jvc2.376 77. Ulrich C. Bichel J. Euvrard S. Guidi B. Proby C.M. Van De Kerkhof P.C.M. Amerio P. …

Decoding Waldenström Macroglobulinemia Through Genomics, Epigenomics and Cellular Interactions

Waldenström macroglobulinemia is a rare lymphoplasmacytic malignancy characterized by bone marrow infiltration and monoclonal immunoglobulin M production. Despite its indolent clinical course, the disease exhibits considerable biological complexity driven by recurrent genetic alterations, dysregulated signaling pathways, and a supportive bone marrow microenvironment. The identification of MYD88 and CXCR4 mutations has significantly advanced understanding of disease pathogenesis, clonal evolution, and treatment response. Additional insights from cytogenetic, epigenetic, and microRNA studies hav

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… Retreatment with the same regimen may be appropriate after a durable remission, while early relapse (<24 months) or refractory disease requires a switch to an alternative class of drugs [ 15 ]. …

Навигация терапевтического ландшафта миеломы: иммунотерапия, микроокружающая среда и сопротивление.

Иммунотерапии, включая клетки химерика антигенного рецептора (CAR) T, биконкретные Т-клеточные агенты (BITEs) и антитело-наркотики (ADC), изменили ландшафт лечения множественной миеломы (MM). Несмотря на высокие показатели первоначальных ответов, достижение долговременной ремиссии по-прежнему сопряжено с трудностями из-за частых рецидивов, вызванных комплексными механизмами терапевтического сопротивления. В этом обзоре мы всесторонне исследуем врожденную устойчивость к опухоли, такую, как врожденный и приобретенный антигенный выход, обусловленный геномными изменениями, структурными вариациями

Bispecific Antibodies and CAR T in Multiple Myeloma: Appropriate Selection of Patients and Sequencing.

T-cell redirecting therapies (TCR) marked a step forward in the treatment of relapsed/refractory multiple myeloma (RRMM). These agents, represented by chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsAbs), proved to ameliorate the prognosis of difficult-to-treat patients in pivotal clinical trials, leading to their introduction into clinical practice. Both strategies rely on recruiting patients' T-cells against specific tumor antigens, with B-cell maturation antigen (BCMA) and G-protein coupled receptor group C family 5 member D (GPRC5D) being the targets most extensively s

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… Salvage therapies including retreatment with BCMA-directed approaches after BCMA CAR-T relapses for multiple myeloma. Blood Adv. 2024 May 14;8(9):2207–16. doi: 10.1182/bloodadvances.2023012066. 117. Jakubowiak AJ, Anguille S, Karlin L, Chari A, Schinke C, Rasche L, et al. …

Advances in Adoptive Cell Therapies in Cancer: From Mechanistic Breakthroughs to Clinical Frontiers and Overcoming Barriers.

Adoptive cell therapies (ACTs) have revolutionized cancer treatment by harnessing the specificity and potency of T lymphocytes. Chimeric antigen receptor (CAR)-T cells have achieved landmark successes in B-cell malignancies and multiple myeloma. Tumor-infiltrating lymphocytes (TILs) and T-cell receptor (TCR)-engineered T cells offer complementary strategies to target solid tumors and intracellular antigens. Despite these advances, ACTs face challenges including cytokine release syndrome, neurotoxicity, on-target/off-tumor effects, manufacturing scalability, and immunosuppressive tumor microenv

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… . | NCT04272151 | BCMA-targeted CAR-T Cells | I | University of California, San Francisco | NCT05577000 | CAR-T cells (Retreatment) | I | Second Affiliated Hospital of Xi’an Jiaotong University | NCT03672253 | BCMA-TGF-BETA CAR-T Cells | I | Medical College of Wisconsin | NCT05976555 | BCMA-targeted …

Targeting autoimmune mechanisms by precision medicine in Myasthenia Gravis.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Cur

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… This is likely due to resurgence of pathogenic B cells, highlighting the need for retreatment ( 64 ). Repopulation of pathogenic versus regulatory B cells is an important factor underlying clinical response to RTX. …

Membranous nephropathy: pathogenesis and treatments.

Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one-third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end-stage renal disease within 10 years. The i

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… Retreatment with rituximab for membranous nephropathy with persistently elevated titers of anti‐phospholipase A2 receptor antibody. Kidney Int. 2019;95(1):233‐234. 171. Hanset N, Esteve E, Plaisier E, et al. …

The prevention of disease relapse after allogeneic hematopoietic cell transplantation in acute myeloid leukemia.

Disease relapse represents by far the most frequent cause of hematopoietic cell transplantation (HCT) failure. Patients with acute leukemia suffering relapse after HCT have limited conventional treatment options with little possibility of cure and represent, de facto, suitable candidates for the evaluation of novel cellular and biological-based therapies. Donor lymphocyte infusions (DLI) has been one of the first cellular therapies adopted to treat post HCT relapse of acute leukemia patients and still now, it is widely adopted in preemptive and prophylactic settings, with renewed interest for

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… In SORMAIN trial, 4 out of 10 disease relapses occurred after the end of sorafenib retreatment and might be preventable by longer maintenance duration. …

Current Overview of Treatment for Metastatic Bone Disease.

The number of patients with bone metastasis increases as medical management and surgery improve the overall survival of patients with cancer. Bone metastasis can cause skeletal complications, including bone pain, pathological fractures, spinal cord or nerve root compression, and hypercalcemia. Before initiation of treatment for bone metastasis, it is important to exclude primary bone malignancy, which would require a completely different therapeutic approach. It is essential to select surgical methods considering the patient's prognosis, quality of life, postoperative function, and risk of pos

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… However, retreatment rates were 2.6 times higher for single-fraction radiotherapy [ 135 ]. Therefore, multiple-fraction radiotherapy that produce a sustained response may be recommended for patients with oligometastatic disease or good prognosis [ 136 , 137 , 138 ]. …

Antibody-Drug Conjugates: Pharmacotherapeutic Properties and Future Perspectives.

Background: The clinical landscape for antibody-drug conjugates (ADCs) is currently experiencing an unprecedented expansion, with more than 20 agents approved to date and hundreds presently under clinical evaluation, underscoring their growing impact in precision oncology. By combining the cytotoxic potency of chemotherapy with the selectivity of monoclonal antibodies, ADCs have redefined targeted cancer therapy. Nevertheless, challenges related to toxicity, resistance, and suboptimal drug delivery continue to limit their full clinical potential. Objectives: This review provides a comprehensiv

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… Retreatment with Brentuximab Vedotin in Patients with Relapsed/Refractory CD30+ Malignancies: A Retrospective Medical Chart Review Study in Spain-The BELIEVE Study. Cancers. 2025;17:1137. doi: 10.3390/cancers17071137. 22. …

Systemic amyloid light-chain amyloidosis beyond ANDROMEDA: Diagnostic challenges and therapeutic updates.

Systemic immunoglobulin light-chain amyloidosis is a rare but life-threatening plasma cell disorder characterized by the production of misfolded monoclonal light chains that deposit as amyloid fibrils, leading to pathologic tissue remodeling and progressive multiorgan dysfunction. Despite substantial therapeutic advances, delayed diagnosis remains common because of nonspecific presentations and the need for coordinated hematologic, pathologic, and organ-specific evaluation. The introduction of daratumumab-based regimens has transformed frontline therapy, whereas advances in cytogenetic profili

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… Nonetheless, a uniformly validated definition for hematologic progression has not been established, and the optimal threshold for initiating retreatment remains guided by FLC kinetics, organ biomarkers, and overall clinical context. …

Cancer Pain Is Not One-Size-Fits-All: Evolving from Tradition to Precision.

Cancer pain remains a significant challenge in oncology, profoundly affecting patients' quality of life, function, and prognosis. Historically under-recognized and managed with a uniform, opioid-centric approach, cancer pain was often inadequately treated. Advances in pain assessment, multimodal analgesia, and supportive care have improved outcomes, yet traditional algorithms frequently fail to address the complex, heterogeneous nature of cancer pain. Contemporary management is shifting toward precision and personalized medicine, integrating genetic, molecular, and biomarker data with individu

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… The standard regimens include 8 Gy in a single fraction for rapid palliation, or multi-fraction schedules such as 20 Gy in 5 fractions or 30 Gy in 10 fractions for patients with longer survival, offering improved local control and reduced retreatment rates. …