Melanoma harboring BRAF mutations frequently develop resistance to BRAF inhibitors, limiting the impact of treatment. Here, we establish a mechanism of resistance and subsequently identified a suitable drug combination to overcome the resistance. Single treatment of BRAF mutant melanoma cell lines with vemurafenib or dabrafenib (BRAF inhibitors) alone or in combination with trametinib (MEK1/2 i...

Aromatase inhibitors (AI) are a standard-of-care treatment for postmenopausal, estrogen receptor-positive breast cancers. Although tumor recurrence on AI therapy occurs, the mechanisms underlying acquired resistance to AIs remain unknown. In this study, we examined a cohort of endocrine-treated breast cancer patients and used a cell line model of resistance to the AI letrozole. In patients trea...

Abstract INTRODUCTION Glioblastoma (GBM) contains cell populations with distinct metabolic requirements, fast-cycling cells harnessing aerobic glycolysis, and treatment-resistant slow-cycling (SCCs) preferentially engaging lipid metabolism. The interaction between immune tumor cells, how their heterogeneity shapes the landscape in GBM has yet to be understood. Objectives: primary objective of t...

Abstract There is increasing evidence that immunotherapies make tumor cells more vulnerable to the host’s own immune system can lead long-term and durable remission. To date, only a small percentage of cancer patients have benefited from this approach advances in field will likely come greater understanding interaction between their targets. T are critical successful anti-tumor response due abi...

Antibodies (Abs) that preferentially target oncogenic receptors have been increasingly used for cancer therapy, but tumors often acquire intrinsic Ab resistance after prolonged and costly treatment. Herein we armed the Ab with IFNβ and observed that it is more potent than the first generation of Ab for controlling Ab-resistant tumors. This strategy controls Ab resistance by rebridging suppresse...

Resistance evolution is a common problem in cancer therapy, especially for genetically heterogeneous tumors that may harbor resistant subpopulations at the onset of treatment. Thus, designing therapeutic regimens that inhibit the spread of resistance is an important problem. Since higher drug concentrations increase the fitness of resistant cells, drug concentrations below the maximum tolerated...

ST1968 is a novel hydrophilic camptothecin (CPT) derivative of the 7-oxyiminomethyl series. Because ST1968 retained ability to form remarkably stable cleavable complexes, this study was done to investigate its preclinical profile of antitumor activity in a large panel of human tumor models, including irinotecan-resistant tumors. Although less potent than SN38 in vitro, i.v. administered ST1968 ...

Hailed as a major step forward in the effort to develop targeted cancer therapies, a recently approved drug for the most common type of skin cancer has been a mixed blessing for patients. Although the initial response is usually dramatic, the tumors often recur as the cancer becomes resistant to treatment. Now researchers at the School of Medicine have identified a second way to block the activ...

Antiangiogenic therapies, such as sunitinib, have revolutionized renal cell carcinoma (RCC) treatment. However, a precarious understanding of how resistance emerges and a lack of tractable experimental systems hinder progress. We evaluated the potential of primary RCC cultures (derived from tumors and tumor grafts) to signal to endothelial cells (EC) and fibroblasts in vitro and to stimulate an...

The analysis of clinical use of neutron therapy with 6 MeV fast neutrons compared to conventional radiation therapy was carried out. The experience of using neutron and mixed neutron and photon therapy in patients with different radio-resistant malignant tumors shows the necessity of further studies and development of the novel approaches to densely-ionizing radiation. The results of dosimetry ...