The HDL particle composition determines its antitumor activity in pancreatic cancer.

Despite enormous efforts to improve therapeutic options, pancreatic cancer remains a fatal disease and is expected to become the second leading cause of cancer-related deaths in the next decade. Previous research identified lipid metabolic pathways to be highly enriched in pancreatic ductal adenocarcinoma (PDAC) cells. Thereby, cholesterol uptake and synthesis promotes growth advantage to and chemotherapy resistance for PDAC tumor cells.

Blockade of Myeloid-Derived Suppressor Cell Expansion with All- Retinoic Acid Increases the Efficacy of Antiangiogenic Therapy.

Intrinsic and adaptive resistance hampers the success of antiangiogenic therapies (AAT), especially in breast cancer where this treatment modality has proven largely ineffective. Therefore, novel strategies to improve the efficacy of AAT are warranted. Solid tumors such as breast cancer are characterized by a high infiltration of myeloid-derived suppressor cells (MDSC), which are key drivers of resistance to AAT.

BET-inhibition by JQ1 promotes proliferation and self-renewal capacity of hematopoietic stem cells.

Although inhibitors of bromodomain and extra terminal domain (BET) proteins show promising clinical activity in different hematologic malignancies, a systematic analysis of the consequences of pharmacological BET inhibition on healthy hematopoietic (stem) cells is urgently needed. We found that JQ1 treatment decreases the numbers of pre-, immature and mature B cells while numbers of early pro-B cells remain constant. In addition, JQ1 treatment increases apoptosis in T cells, all together leading to reduced cellularity in thymus, bone marrow and spleen.

Acute Myelogenous Leukemia and its Microenvironment: A Molecular Conversation.

Survival of patients with acute myelogenous leukemia (AML) depends on our ability to prevent relapse in patients that achieved complete remission after intensive chemotherapy. While studies focusing on the malignant clone brought many advances in understanding AML biology and chemoresistance, little improvement has been made in eliminating the last bastion of malignant cells, the minimal residual disease (MRD). Inspired by Sir Paget's "soil and seed" hypothesis, it is becoming more clear that there is constant feedback between the malignant clone and the leukemic microenvironment.

Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs.

Anti-angiogenic therapies were approved for different cancers. However, significant primary and secondary resistance hampers efficacy in several tumor types including breast cancer. Thus, we need to develop clinically applicable strategies to enhance efficacy of anti-angiogenic drugs.

Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma.

Acute myeloid leukemia (AML) represents a clonal disease of hematopoietic progenitors characterized by acquired heterogenous genetic changes that alter normal mechanisms of proliferation, self-renewal, and differentiation.(1) Although 40% to 45% of patients younger than 65 years of age can be cured with current therapies, only 10% of older patients reach long-term survival.(1) Because only very few novel AML drugs were approved in the past 2 decades, there is an urgent need to identify novel targets and therapeutic strategies to treat underserved AML patients.