The AKT pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation and has been shown to have prognostic significance in a number of cancers. Recently, the inventors have identified several functions of the AKT pathway in certain cancers, such as extrahepatic cholangiocarcinoma (EHCC).
B-cell chronic lymphocytic leukemia (B-CLL) is a cancer characterized by a progressive accumulation of functionally incompetent lymphocytes. Despite high morbidity and mortality, the only available potential cure is allogeneic hematopoietic stem cell transplantation (alloHSCST). However, there is less than a 50% chance of finding a matching bone marrow or blood donor for B-CLL patients. Other clinically tested targeted therapies such as rituximab and alemtuzumab target both malignant and normal B cells, resulting in immunosuppression.
Molecular profiling with high throughput assays has gained utility in the management of select cancer patients and several gene expression-based assays are now marketed for improved prognostic accuracy for patients with cancer.
The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy.
Neuroblastoma is a rare pediatric cancer that affects one in every hundred thousand children under the age of fifteen in the United States. Current standards of care are chemotherapy and surgery, followed by stem-cell treatments, radiation and anti-ganglioside antibody therapy, which yield an average three-year survival rate of 10-45%. This demonstrates a need for more effective therapies.
Alterations in microRNAs (miRNAs), a type of small non-coding RNAs, have been reported in cells/tumors subjected to radiation exposure, implying that miRNAs play an important role in cellular stress response to radiation. NCI researchers evaluated small non-coding RNAs, long non-coding RNAs (lncRNA), and mRNA, as potential non-invasive biomarkers for radiation biodosimetry. While the use of miRNAs as radiation biomarkers has been reported, the integrated use of miRNAs, mRNAs and lncRNAs to accurately determine radiation doses is novel and has not been published.
The high mortality rate from ovarian cancers can be attributed to late-stage diagnosis and lack of effective treatment. Despite enormous effort to develop better targeted therapies, platinum-based chemotherapy still remains the standard of care for ovarian cancer patients, and resistance occurs at a high rate. One of the rate limiting factors for translation of new drug discoveries into clinical treatments has been the lack of suitable preclinical cancer models with high predictive value.
Optical traps (optical tweezers) have a focused laser beam able to trap a small bead at its focus, and are used to measure the microrheology of gels and other materials. They have recently been used to characterize properties of living cells, however issues of image spatial resolution and limited depth of interrogation have prevented application of an optical trap to measure microrheological (flow of matter) properties in complex (non-uniform) materials, such as multi-cellular systems or living organisms.
Chimeric antigen receptors (CARs) are hybrid proteins consisting of an antibody binding fragment fused to protein signaling domains that cause T-cells which express the CAR to become cytotoxic. Once activated, these cytotoxic T-cells can selectively eliminate the cells which they recognize via the antibody binding fragment of the CAR. By engineering a T-cell to express a CAR that is specific for a certain cell surface protein, it is possible to selectively target those cells for destruction. This is a promising new therapeutic approach known as adoptive cell therapy.
The glycoprotein CD56, also known as a neural cell adhesion molecule (NCAM), plays an important role in normal physiological functions. It is expressed in low levels in normal cells such as neurons, glia, skeletal muscle and natural killer cells.