Latest Research
All publications from the Cancer3.AI database, newest first.
Emerging chemical strategies for CD38 inhibition: restoring NAD+ metabolism and disease control.
Zhang Z, et al
A new review published in Bioorganic & Medicinal Chemistry examines emerging chemical strategies targeting CD38, a multifunctional enzyme that accelerates the breakdown of NAD+, a molecule essential for cellular energy, immune function, and mitochondrial health. Excessive CD38 activity has been linked to NAD+ depletion during aging, chronic inflammation, and tumor growth, creating conditions that favor mitochondrial dysfunction and immune suppression in cancer patients. Researchers systematically catalogued two broad classes of CD38 inhibitors: covalent inhibitors derived from nucleotide and nucleoside scaffolds that permanently block the enzyme, and versatile non-covalent inhibitors including NAD+ analogues, fully synthetic compounds, and natural products that reversibly restore NAD+ homeostasis. Both approaches demonstrated meaningful efficacy in elevating tissue NAD+ levels and rebalancing immune-metabolic function in preclinical models. This comprehensive chemical landscape offers clinicians and drug developers a rich toolkit for investigating CD38 biology and advancing therapeutic candidates for age-related diseases, inflammatory conditions, and cancer.
Bioorganic & medicinal chemistry
Source →Organ-specific local cytokine release syndrome after anti-CD19 CAR-T therapy with salivary gland involvement: a case report, literature review, and a diagnostic alert for tocilizumab-associated cervical swelling.
Maggi R, et al
This case report describes two patients with refractory diffuse large B-cell lymphoma (DLBCL) who developed an unusual complication called localized cytokine release syndrome (L-CRS) involving the salivary glands following anti-CD19 CAR-T cell therapy. Both patients experienced sudden, painful bilateral swelling of the parotid and/or submandibular glands shortly after their systemic CRS was treated with tocilizumab, with infectious, autoimmune, and obstructive causes ruled out by ultrasound and clinical evaluation. Due to the rapid progression of swelling and risk of airway obstruction, corticosteroids were administered and led to prompt resolution in both cases. The authors reviewed published literature on craniocervical L-CRS and issued a critical diagnostic alert: clinicians must distinguish between true L-CRS and a tocilizumab-associated infusion or hypersensitivity reaction when cervical swelling appears shortly after tocilizumab administration. This report is clinically significant because it demonstrates that salivary gland involvement in L-CRS can occur even without detectable tumor in the neck region, and that rapid recognition and treatment are essential to prevent life-threatening airway compromise in CAR-T therapy recipients.
Annals of hematology
Source →Phase 1 Dose-Escalation Study of [225Ac]Ac-PSMA I&T in Patients with Metastatic Castration-Resistant Prostate Cancer: An Analysis of Safety, Tolerability, and Dosimetry.
Ling SW, et al
This phase 1 clinical trial investigated the safety, tolerability, and radiation dosimetry of [225Ac]Ac-PSMA I&T, an alpha-particle radiopharmaceutical targeting prostate-specific membrane antigen, in nine patients with metastatic castration-resistant prostate cancer. Patients received up to two cycles of escalating radioactivity doses ranging from 8 to 12 MBq, with adverse events closely monitored and dosimetry assessed through blood sampling, urine collection, and whole-body imaging over up to ten days. The most common side effect was dry mouth (xerostomia), reported in 89% of patients, and two dose-limiting toxicities occurred at the 12 MBq level, establishing 10 MBq as the recommended dose for future phase 2 trials. Nearly half of patients (44%) achieved a clinically meaningful decline in prostate-specific antigen levels of at least 50%, and the median overall survival was 15 months, supporting the potential anti-tumor activity of this approach. A key technical finding was that quantitative dosimetry via SPECT/CT imaging is not currently feasible for actinium-225, underscoring the need for improved imaging methods to better guide and personalize future treatments.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Source →Proton beam therapy for external auditory canal and middle ear cancers.
Machida M, et al
A Japanese research team conducted a retrospective study to evaluate the effectiveness and safety of proton beam therapy (PBT) for two rare and difficult-to-treat cancers: external auditory canal cancer (EACC) and middle ear cancer (MEC), enrolling 15 patients treated between December 2009 and August 2018. Most patients also received chemotherapy — either systemic or via intra-arterial infusion — alongside radiation, with a median follow-up of 60 months. At three years, the overall survival rate was 65%, local tumor control was achieved in 66.7% of patients, and progression-free survival reached 53.3%, indicating clinically meaningful disease management in this challenging anatomical region. Regarding safety, four patients experienced grade 3 hearing loss as a late side effect, but all had pre-existing hearing impairment before treatment began, and no grade 4 or higher toxicities were recorded throughout the follow-up period. These results support proton beam therapy as an effective and well-tolerated treatment option for patients with these rare ear cancers, demonstrating that PBT can be safely combined with chemotherapy without severe added toxicity.
Journal of radiation research
Source →Middle Ear Bacterial Colonization and Recurrence of Radiation-Induced OME: A Prospective Study.
Chen M, et al
Researchers conducted a prospective multicenter cohort study investigating the bacteriological profile of middle ear fluid in nasopharyngeal carcinoma (NPC) patients who developed otitis media with effusion (OME) following radiotherapy, and whether bacterial colonization in the middle ear raises the risk of early disease recurrence. The study enrolled 93 patients with radiation-induced OME (RI-OME) and 115 patients with non-radiation-induced OME, all of whom underwent tympanocentesis — a procedure to drain fluid from the middle ear — with RI-OME patients followed for 24 weeks afterward. Patients with RI-OME had nearly five times higher odds of bacterial growth in their middle ear fluid compared to those without a radiation history, and their infections more frequently involved opportunistic pathogens and drug-resistant bacteria, reflecting the immunologically altered environment caused by prior radiotherapy. Mucoid effusion was identified as a strong independent risk factor for bacterial positivity in RI-OME, while male sex and bacterial colonization were each associated with early recurrence of fluid within the first four weeks after tympanocentesis. However, neither factor independently predicted overall recurrence across the full 24-week follow-up, leaving unanswered whether targeted antibiotic therapy could meaningfully reduce long-term recurrence rates. These findings highlight the distinct microbial landscape of radiation-induced middle ear disease and underscore the need for further research into antibacterial treatment strategies for NPC survivors experiencing persistent or recurrent OME.
The Laryngoscope
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