CD Protein Inhibitors 

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  • ||||||||||  PPMX-T003 / Fujifilm Holdings
    Journal:  Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia. (Pubmed Central) -  Jul 29, 2024   
    We also found that the influx of extracellular amino acids via LAT1 stimulated sensitivity to PPMX-T003. Taken together, we discovered that the amount of extracellular amino acid influx through LAT1 was the key environmental factor determining the iron dependency of ANKL cells via adjustment of their mTOR/Myc activity, which provides a good explanation for the different sensitivity to PPMX-T003 between liver- and spleen-resident ANKL cells, as the liver sinusoid contains abundant amino acids absorbed from the gut.
  • ||||||||||  Ibrance (palbociclib) / Pfizer, Xospata (gilteritinib) / Astellas
    Journal:  Combination of menin and kinase inhibitors as an effective treatment for leukemia with NUP98 translocations. (Pubmed Central) -  Jul 29, 2024   
    Despite inhibiting two unrelated kinases, when Palbociclib or Gilteritinib were combined with the menin inhibitor, they affected similar pathways relevant to leukemogenesis, including cell cycle regulation, cell proliferation and differentiation. This study provides strong rationale for clinical translation of the combination of menin and kinase inhibitors as novel treatments for NUP98-r leukemia, supporting the unexplored combinations of epigenetic drugs with kinase inhibitors.
  • ||||||||||  linvoseltamab (REGN5458) / Regeneron, Sanofi
    Journal:  Linvoseltamab for Treatment of Relapsed/Refractory Multiple Myeloma. (Pubmed Central) -  Jul 29, 2024   
    No new safety signals were identified. Linvoseltamab 200 mg induced deep and durable responses, with a median DOR of 29.4 months, in patients with RRMM with an acceptable safety profile.
  • ||||||||||  Yescarta (axicabtagene ciloleucel) / Gilead
    Journal, CAR T-Cell Therapy:  Identification of a clinically efficacious CAR T cell subset in diffuse large B cell lymphoma by dynamic multidimensional single-cell profiling. (Pubmed Central) -  Jul 29, 2024   
    Using independent datasets, we validate that CD8-fit T cells (1) are present premanufacture and are associated with clinical responses in individuals treated with axicabtagene ciloleucel, (2) longitudinally persist in individuals after treatment with CAR T cells and (3) are tumor migrating cytolytic cells capable of intratumoral expansion in solid tumors. Our results demonstrate the power of multimodal integration of single-cell functional assessments for the discovery and application of CD8-fit T cells as a T cell subset with optimal fitness in cell therapy.
  • ||||||||||  Keytruda (pembrolizumab) / Merck (MSD), Opdivo (nivolumab) / BMS
    Review, Journal:  Immunotherapy for head and neck cancer: Fundamentals and therapeutic development. (Pubmed Central) -  Jul 29, 2024   
    The results of these trials are numerous, both positive and negative, and a comprehensive understanding of this wide range of completed and ongoing clinical trials is critical to a systematic and comprehensive understanding of their scope and lessons learnt. In this article, after outlining the concepts of ``cancer immune cycle,'' ``cancer immune editing,'' and ``tumor microenvironment'' to provide an understanding of the basics of cancer immunity, we summarize the basics and clinical trial data on representative immune checkpoint inhibitors used in various cancer types, as well as recent therapeutic developments in cancer immunotherapy and the current status of these new treatments.
  • ||||||||||  Ibrance (palbociclib) / Pfizer
    Journal, Tumor cell:  A deep learning model of tumor cell architecture elucidates response and resistance to CDK4/6 inhibitors. (Pubmed Central) -  Jul 29, 2024   
    To elucidate the underlying mechanisms, we constructed an interpretable deep learning model of the response to palbociclib, a CDK4/6i, based on a reference map of multiprotein assemblies in cancer...Validated assemblies relate to cell-cycle control, growth factor signaling and a histone regulatory complex that we show promotes S-phase entry through the activation of the histone modifiers KAT6A and TBL1XR1 and the transcription factor RUNX1. This study enables an integrated assessment of how a tumor's genetic profile modulates CDK4/6i resistance.
  • ||||||||||  sunitinib / Generic mfg.
    Journal:  HDAC8 Enhances the Function of HIF-2? by Deacetylating ETS1 to Decrease the Sensitivity of TKIs in ccRCC. (Pubmed Central) -  Jul 29, 2024   
    Here, genome-wide CRISPR-based screening to reveal that HDAC8 is involved in decreasing the sensitivity of ccRCC cells to sunitinib is applied...Finally, HDAC8-in-PROTACs to optimize the effects of HDAC8 inhibitors through degrading HDAC8 and overcoming the resistance of ccRCC to TKIs are synthesized. Collectively, the results revealed HDAC8 as a potential therapeutic candidate for resistance to ccRCC-targeted therapies.
  • ||||||||||  Rituxan (rituximab) / Roche
    Journal:  Marine sponge-derived alkaloid inhibits the PI3K/AKT/mTOR signaling pathway against diffuse large B-cell lymphoma. (Pubmed Central) -  Jul 29, 2024   
    Further experiments demonstrated that AP-48 exerted its anti-DLBCL effects through the PI3K/AKT/mTOR pathway, and that the PI3K agonist YS49 partially alleviated the inhibition of cell proliferation and apoptosis induced by AP-48. Finally, in a tumor xenograft model, AP-48 inhibited tumor growth and promoted apoptosis in tumor tissues, indicating its therapeutic potential in DLBCL.
  • ||||||||||  Kisqali (ribociclib) / Novartis
    Journal:  The NEOLETRIB trial: neoadjuvant treatment with Letrozole and Ribociclib in ER-positive, HER2-negative breast cancer. (Pubmed Central) -  Jul 29, 2024   
    P2
    Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Our findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination and give new insights into the intra-tumoral changes during this treatment.Trial registration number: NCT05163106 (ClinicalTrials.gov).
  • ||||||||||  Review, Journal:  Novel treatments for immune thrombocytopenia: targeting platelet autoantibodies. (Pubmed Central) -  Jul 29, 2024   
    Treatments outlined in this review include a) FcRn antagonists (efgartigimod), b) complement inhibitors (sutimlimab), c) B-cell directed therapies such as BTK inhibitors (rilzabrutinib), anti-BAFF agents (belimumab, ianalumab), and Syk inhibitors (fostamatinib, sovleplenib), d) plasma-cell directed therapies (daratumumab, bortezomib), and e) cellular therapeutic products. Platelet antibodies are often elusive in ITP; yet novel treatments targeting this pathway reinforce their role in the pathogenesis of this autoimmune platelet disorder.
  • ||||||||||  Journal, Metastases:  Approaches to Treating High Risk and Advanced Renal Cell Carcinoma (RCC): Key Trial Data That Impacts Treatment Decisions in the Clinic. (Pubmed Central) -  Jul 29, 2024   
    Subsequently, adjuvant pembrolizumab has shown a benefit in overall survival, whereas trials of neoadjuvant and adjuvant nivolumab, adjuvant atezolizumab, and adjuvant ipilimumab plus nivolumab have all been negative...The CARMENA study raised important questions about the role of cytoreductive nephrectomy given the advances in VEGFR TKI therapy but was characterized by accrual difficulties and a significant number of patients not receiving treatment according to the study protocol. Two ongoing studies (NORDIC-SUN and PROBE) seek to further address the role of cytoreductive nephrectomy in the doublet therapy era.
  • ||||||||||  Tevimbra (tislelizumab-jsgr) / BeiGene
    Review, Journal:  Amelanotic primary cervical malignant melanoma: A case report and review of literature. (Pubmed Central) -  Jul 29, 2024   
    Due to the lack of established therapeutic guidelines, empirical information from limited available studies does not provide the rationale for treatment-decision making. By integrating 'omics' technologies and patient-derived xenografts or mini-patient-derived xenograft models this will help to identify selective therapeutic window(s) and screen the appropriate therapeutics for targeted therapies, immune checkpoint blockade or combination therapy strategies effectively and precisely that will ultimately improve patient survival.
  • ||||||||||  Prolia (denosumab) / Amgen, Ibrance (palbociclib) / Pfizer, Kisqali (ribociclib) / Novartis
    Retrospective data, Journal, Metastases:  Exploring the Clinical Impact of RANK Pathway Inhibition in Advanced Breast Cancer: Insights From a Retrospective Study on CDK4/6 Inhibitors and Antiresorptive Therapy. (Pubmed Central) -  Jul 29, 2024   
    This study highlights the potential clinical relevance of the RANK pathway in BC treatment, and our findings suggest that denosumab may offer significant benefits in terms of PFS and OS for certain subgroups, particularly those with HER2 scores of 1, patients under 60, and those with endocrine-resistant BC. In conclusion, considering that RANK pathway status may be a predictive biomarker for CDK4/6i treatment and may cause treatment resistance, our results demonstrate the clinical relevance of the combination of CDK4/6i + ET with RANKL inhibition.
  • ||||||||||  Rituxan (rituximab) / Roche
    Journal:  Paraneoplastic pemphigus with airway involvement. (Pubmed Central) -  Jul 29, 2024   
    We report a case of paraneoplastic pemphigus presenting with acute hypoxemic respiratory failure due to bronchiolitis obliterans which improved with high dose systemic corticosteroids, rituximab, niacinamide and doxycycline. This is the first report, to our knowledge, of paraneoplastic pemphigus with airway involvement which included niacinamide and doxycycline as therapy and demonstrated treatment response.
  • ||||||||||  Gazyva (obinutuzumab) / Roche, Biogen, Rituxan (rituximab) / Roche
    Journal:  The 508th case: recurrent edema of bilateral lower extremities with proteinuria (Pubmed Central) -  Jul 29, 2024   
    This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.
  • ||||||||||  linrodostat (BMS-986205) / BMS, Ono Pharma, Opdivo (nivolumab) / BMS
    Trial completion date, Trial termination, Trial primary completion date:  Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck (clinicaltrials.gov) -  Jul 28, 2024   
    P2,  N=45, Terminated, 
    Recruiting --> Active, not recruiting | Trial completion date: Dec 2027 --> Jul 2027 Trial completion date: Dec 2025 --> Jun 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Jun 2024; toxicity - per sponsor
  • ||||||||||  Tevimbra (tislelizumab-jsgr) / BeiGene, BGB-R046 / BeiGene
    Enrollment open, Combination therapy, Monotherapy, Metastases:  BGB-R046-101: A Study of BGB-R046 as Monotherapy and in Combination With Tislelizumab in Solid Tumors (clinicaltrials.gov) -  Jul 28, 2024   
    P1,  N=74, Recruiting, 
    Trial completion date: Dec 2025 --> Jun 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Jun 2024; toxicity - per sponsor Not yet recruiting --> Recruiting
  • ||||||||||  Adcetris (brentuximab vedotin) / Takeda, Pfizer, Imbruvica (ibrutinib) / AbbVie, J&J
    Journal:  Brentuximab Vedotin Plus Ibrutinib in Relapsed and Refractory Hodgkin Lymphoma. (Pubmed Central) -  Jul 28, 2024   
    Our findings support the use of PD-1 blockade in HIV-cHL for the same indications as the general population with cHL. The combination of BV and ibrutinib was active in r/r HL; however, given significant toxicity, it cannot be recommended for future development.
  • ||||||||||  cytarabine / Generic mfg., Rituxan (rituximab) / Roche, Imbruvica (ibrutinib) / AbbVie, J&J
    Review, Journal, Heterogeneity:  SOHO State of the Art Updates and Next Questions: Treatment Evolution of Mantle Cell Lymphoma: Navigating the Different Entities and Biological Heterogeneity of Mantle Cell Lymphoma in 2024. (Pubmed Central) -  Jul 28, 2024   
    In parallel to the demonstration of benefit using combination therapy with rituximab plus high-dose cytarabine (R-AraC) as well as dose intensive therapy-autologous stem cell transplantation (DIT-ASCT) consolidation and maintenance, it became clear over the last 2 decades that MCL is a highly heterogenous disease at the molecular level, explaining differences observed in clinical behavior and response to therapy...The era of integrating novel agents into our prior standard of care (SOC) has begun with a confirmed benefit, for example, ibrutinib (Ib) in the TRIANGLE study, defining the first new potential SOC in younger patients in over 30 years...Taking into account the biological diversity of MCL is now feasible in routine clinical practice and has already helped recognize what not to do for HR patients (i.e., avoid intensive induction chemotherapy and/or ASCT for p53 mutated patients) as well as identify promising novel options. Ongoing and future work will help expand on these dedicated approaches, to further improve the management and outcomes of all MCL patients.