General AML

AACR 2017: Poster 4059/29 – KPC34 for therapy in AML patients

On Tuesday 4th April, at the 107th American Association for Cancer Research (AACR) annual meeting in Washington, DC, USA, there was a poster session focused on “Combination Therapies and Approaches to Sensitize Cancer Cells to Drugs”. During this session, a poster (4059/29) titled “KPC34: a co-drug that combines a DNA damaging agent with a targeted therapy for the treatment of AML” by Gregory L. Kucera and colleagues from Wake Forest School of Medicine, North Carolina, was on display.

Standard chemotherapy with Cytarabine (Ara-C) in Acute Myeloid Leukemia (AML) is hindered by chemoresistance which leads to relapse in patients. Chemoresistance can occur due to several mechanisms including reduced activation of Ara-C via down-regulated Deoxycytidine Kinase (dCK) levels or decreased uptake via lowered Equilibrative Nucleoside Transporter 1 (ENT-1) levels. Kucera et al. aimed to assess the efficacy of KPC34, a novel synthetic phospholipid/deoxycytidine analog conjugate, in AML.

The key results were:
  • Median survival of KPC34-treated and Ara-C treated mice injected with OCI-AML-3 cells (AML cell line); 44.5 vs 25 days; P = 0.0033
  • Retreatment of the KPC34 mice with additional KPC34 resulted in a median survival time of 78.5 days; P = 0.0028
  • Median survival in mice treated with KPC34 plus doxorubicin (dox) and Ara-C plus dox; 39 vs 22 days, P = 0.0365
  • KPC34 showed a reduction in leukemic burden in the liver and spleen in Patient-Derived Xenograft (PDX) murine model
  • Treatment of OCI-AML3 cells with KPC34 led to an inhibition of Protein Kinase C (PKC) signaling

In summary, KPC34 can inhibit PKC and cause DNA termination. The authors concluded by suggesting that KPC34 has the “potential to replace Ara-C-based leukemia treatment regimens as a single agent or in combination” therapy for AML.

References
  1. Kucera G.L. et al. KPC34: a co-drug that combines a DNA damaging agent with a targeted therapy for the treatment of AML [ Poster]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; 2017. Poster nr [4059/29].