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Poly-ADP ribose polymerase-1 (PARP-1) is a critical enzyme involved in DNA repair.  The inhibition of PARP has emerged as a promising strategy in cancer therapy.  Numerous PARP inhibitors have been developed and advanced into clinical trials, both for use as single agents in specific patient populations and as combination therapies with various chemotherapeutics.  The induction of strand break damage to DNA, as has been demonstrated in cancer cells treated with O2-arylated diazeniumdiolates, coupled with inhibition of DNA repair by PARP inhibitors, represents a novel rational

Immune checkpoint inhibitors (e.g. CTLA-4, PD-L1) have recently shown significant promise in the treatment of cancer.  However, when used alone, these checkpoint inhibitors are limited by the absence or repression of immune cells within the targeted cancer.  For those cancers associated with these limited immune systems, there remains a need for effective therapies.  Agents capable of recruiting and activating immune cells to these types of cancers could extend the overall and complete response rates of combination therapies within the immunooncology domain. 

Angiogenesis is the formation of new blood vessels from pre-existing blood vessels. Angiogenesis occurs during normal growth and development (physiological angiogenesis) and during the growth of solid tumors (pathological angiogenesis). CD276, also known as B7-H3, is a cell surface tumor endothelial marker that is highly expressed in the tumor vessels of human lung, breast, colon, endometrial, renal, and ovarian cancer, but not in the angiogenic vessels of normal, healthy tissue.

The tumor microenvironment consists of a heterogenous population of cells which includes tumor cells and tumor-associated stroma cells (TASCs). The TASCs promote tumor angiogenesis, proliferation, invasion and metastasis. Because stroma cells are found in both healthy and cancerous tissue, targeting the tumor stroma has been difficult due to the lack of targets with high tumor specificity.

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. 

Angiogenesis is the formation of new blood vessels from pre-existing blood vessels. Angiogenesis occurs during normal growth and development, where it is known as physiological angiogenesis, and during the growth of solid tumors, where it is known as pathological angiogenesis. CD276, also known as B7-H3, is a cell surface tumor endothelial marker that is highly expressed in the tumor vessels of human lung, breast, colon, endometrial, renal, and ovarian cancer, but not in the angiogenic vessels of healthy tissue.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths in developed countries.  Despite the availability of several synergistic, targeted therapy regiments, the 5-year survival rate for NSCLC is only 15%.  The poor prognosis of NSCLS is due in part to limitations of current treatments, which do not trigger an immune response against NSCLC, nor can they be directly delivered into the lungs.  

HMGN polypeptides belong to the high mobility group (HMG) family of chromosomal binding peptides. HMGN polypeptides typically function inside the cell nucleus to bind to DNA and nucleosomes and regulate the transcription of various genes. HMGN polypeptides also can be released by peripheral blood mononuclear cells. However, the extracellular release of a HMGN polypeptide initiates activation of the immune system. Therefore, it has potential use as a biological therapeutic for stimulating an immune response.

The NCI Laboratory of Cancer Biology and Genetics seeks parties interested in collaborative research to further develop this mouse model of triple-negative breast cancer (TNBC) to study cancer biology and for preclinical testing.  As a Research Tool, patent protection is not being pursued for this technology; more information to access this strain can be found here: https://www.jax.org/strain/030386.

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.