Nanox · TOP2A · Small Molecule
doxorubicin is a small molecule developed by Nanox. It is approved for therapeutic indications via injectable (others).
| Brand Names | doxorubicin, Nanox, Doxonax |
| Company | Nanox |
| Drug Class | Small Molecule |
| Molecular Target | TOP2A |
| Route | Injectable (Others) |
| Status | Approved |
doxorubicin acts on 1 molecular target:
| TOP2A | DNA topoisomerase II alpha (TOP2alpha, TOPIIA) |
doxorubicin is developed for 1 unique indication across 1 therapeutic area.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Kaposi's sarcoma | ✓ Approved |
Srinivasan Sushmitha Grama SG, Kamens Jennifer L JL, Marks Lianna J LJ, Balagtas Jay M S JMS et al.
Saravanakumar Kandasamy K, Hu Xiaowen X, Shanmugam Sabarathinam S, Chelliah Ramachandran R et al.
Samudrala Anuveda Sree AS, Nagaraju Ganji Purnachandra GP, Malla RamaRao R
Breast cancer is the most frequently reported cancer in women, with high mortality and morbidity globally. Paclitaxel, doxorubicin, tamoxifen, cisplatin, and 5-fluorouracil are cornerstones of standard-of-care treatment for primary and advanced breast cancers, targeting distinct molecular mechanisms. However, the evolution of acquired resistance primarily leads to treatment failure and progression to metastasis, ultimately to patient mortality. Furthermore, their effectiveness is limited by potential toxicities in various organs. These limitations present an extreme challenge for the management of breast cancer at the advanced stage. This review uncovers recent updates on acquired resistance mechanisms toward standard-of-care treatments driven by deeply rooted heterogeneity and aggressive nature through direct counteracting of its core action, hyperactivation of survival pathways, silencing of core cell death pathways, derepressing the expression of multidrug resistance proteins, metabolic reprogramming, epigenetic modifications, and exosome-mediated horizontal transfer of resistance phenotype. In addition, we discuss recent updates on potential strategies to overcome resistance and toxicities induced by standard-of-care treatments. Ultimately, this review helps to identify novel strategies targeting pathways to reverse resistance and reduce toxicity in breast cancer patients.
Ibrahim Rowan A E RAE, Ahmed Basant Atef BA, Bahr Ahmed Reda AR, ElShazly Mohammed M
Classic Hodgkin lymphoma (cHL) generally has favorable outcomes with frontline ABVD chemotherapy; however, 15-30% of advanced-stage patients experience relapse. While PD-1 inhibitors like pembrolizumab have shown promise in relapsed/refractory cHL, immune-related adverse events remain incompletely characterized. We report a 56-year-old male with stage IV nodular sclerosis cHL who relapsed after multiple treatment lines including ABVD, DHAP, brentuximab vedotin, and ICE. Following pembrolizumab plus GVD (gemcitabine, vinorelbine, liposomal doxorubicin), he achieved complete metabolic response. Subsequently, he developed marked leukocytosis (WBC: 63,000/μL) with profound eosinophilia (53,000/μL), meeting criteria for hypereosinophilic syndrome (HES). Molecular workup revealed FIP1L1-PDGFRA rearrangement in 2% of cells. The patient required hospitalization for dehydration, renal dysfunction, and anasarca, and was managed with corticosteroids after hydroxyurea intolerance. This case uniquely documents HES as a rare complication of pembrolizumab/GVD in multiply relapsed cHL, occurring after extensive prior therapy that may have contributed to its development. The molecular findings suggest potential therapeutic avenues. Clinicians should maintain vigilance for eosinophilia during PD-1 inhibitor therapy, as HES management may take precedence over ongoing immunotherapy.
Fernandes Isabel V IV, Melo Sara S, Sousa Gabriela M GM, Pazos Maria Isabel MI et al.
Chemotherapy-induced peripheral neuropathy (CIPN) is among the most prevalent and clinically significant toxicities from systemic cancer treatments, with taxanes being a leading cause. It is characterised by a length-dependent, predominantly sensory axonal neuropathy that can stabilise or improve after treatment discontinuation. However, the clinical course can be profoundly altered by underlying peripheral nerve pathology. We report the case of a 68-year-old woman with luminal B, HER2-negative breast cancer who developed severe peripheral neuropathy during adjuvant chemotherapy with doxorubicin/cyclophosphamide followed by weekly paclitaxel. Treatment was discontinued after 9 of 12 planned paclitaxel cycles due to grade 3 peripheral neuropathy ( Common Terminology Criteria for Adverse Events (CTCAE) v5.0). Despite cessation of the offending agent and initiation of duloxetine, symptoms continued to worsen, with progressive motor impairment and significant gait instability. Nerve conduction studies revealed a severe sensorimotor demyelinating polyneuropathy, atypical for the predominantly axonal pattern of taxane-induced CIPN. Inflammatory, infectious, paraneoplastic, and metabolic causes were excluded, and empirical corticosteroids and intravenous immunoglobulin proved ineffective. Genetic testing identified a peripheral myelin protein 22 (PMP22) duplication (17p11.2), confirming Charcot-Marie-Tooth disease type 1A (CMT1A), a hereditary demyelinating neuropathy previously subclinical. This case report underscores the value of serial clinical and electrophysiological assessment when neuropathy is atypical, disproportionately severe, or refractory to standard treatment.
Ichikawa Satoshi S, Suzuki Yutaka Y, Tanaka Yuya Y, Kanba Keita K et al.
Hemophagocytic lymphohistiocytosis (HLH) complicating classic Hodgkin lymphoma (HL-HLH) is a rare but frequently life-threatening condition that is strongly associated with Epstein-Barr virus (EBV) infection, particularly in the mixed-cellularity and lymphocyte-depleted subtypes. No consensus has been reached regarding treatment for HL-HLH, and the myelotoxicity induced by etoposide-based HLH-directed therapy precludes its safe addition to intensive lymphoma-directed chemotherapy, particularly in older patients. We here report the case of a male in his early 70s with advanced EBV-positive mixed-cellularity classic Hodgkin lymphoma (CHL) who presented with cervical lymphadenopathy, fever, hepatosplenomegaly, and a markedly elevated soluble interleukin-2 receptor (sIL-2R) level, along with a high peripheral blood EBV DNA load. EBV-encoded small RNA in situ hybridization confirmed EBV positivity in lymphoma cells. His fever was steroid-refractory, and chemotherapy with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (BV-AVD) was initiated immediately following the diagnosis was confirmed. However, the persistent high fever did not resolve, and progressive cytopenia, marked hyperferritinemia, and further increase in sIL-2R levels were observed. Repeat bone marrow examinations revealed macrophage activation with hemophagocytosis, confirming HLH as a complication. Rituximab was promptly administered, and the fever resolved within 3 days. Furthermore, ferritin, sIL-2R, and lactate dehydrogenase levels substantially declined within 1 week, with peripheral blood EBV DNA becoming undetectable. BV-AVD was continued without major complications and led to a complete response after six cycles. Rituximab may represent a strategically timed and reasonable adjunctive intervention for EBV-driven HL-HLH that is refractory to, or develops following, chemotherapy for CHL.
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