Myriad Pharmaceuticals is developing MPI-0485520 and other inhibitors of IKKE, a recently identified oncogene playing a role in controlling proliferation of certain cancer cells through regulation of constitutive NFkappaB activity.

Midkine is a heparin-binding growth factor with mitogenic activity for fibroblasts and neuroectoderm cells. This multifunctional cytokine is expressed during midgestation but is highly restricted in normal adult tissues. Midkine's role in early cancer formation has been validated in clinical studies. Midkine levels in the circulation are greatly elevated in the early stages of cancer formation and high midkine levels have been linked to poor prognosis in numerous malignancies.

Chromosomal rearrangements enhance the activity of receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) and are implicated in various malignancies, including non-Hodgkin's lymphoma (NHL), neuroblastoma and non-small cell lung cancer (nsclc).

Nuclear factor, interleukin 3 regulated (NFIL3), or E4BP4 , a basic leucine zipper (bZIP) transcription factor, appears to mobilize the immune system by causing circulating stem cells to become natural killer (NK) cells. Using E4BP4-null mice, investigators at University College London Institute of Child Health and Great Ormond Street Hospital for Children (London, UK) showed that overexpression of E4bp4 was sufficient to increase NK cell production from hematopoietic progenitor cells (stem cells), a finding that may lead to the development of pharmacologic approaches to increase production of NK cells to treat a variety of diseases including cancer (Gascoyne DM, etal, Nat Immunol, 13 Sep 2009; epub ahead of print).

Investigators at Stanford’s School of Medicine isolated and characterized a tumor-initiating cell (stem cell) subpopulation in primary human bladder cancer with potential prognostic and therapeutic value for invasive bladder cancer. http://med.stanford.edu/ism/2009/august/bladder-cancer.html. Although molecular analysis of more than 300 bladder cancer specimens revealed heterogeneity among activated oncogenic pathways in these cells, a unique bladder stem cell gene signature was identified, which effectively distinguishes muscle-invasive bladder cancer with worse clinical prognosis from superficial cancer and also predicts progression of a subset of recurring non-muscle-invasive cancer. CD47, a protein that provides an inhibitory signal for macrophage phagocytosis, is highly expressed in bladder tumor-initiating cells (stem cells) compared with the rest of the tumor. Blockade of CD47 by a MAb resulted in macrophage engulfment of bladder cancer cells in vitro. http://www.pnas.org/content/early/2009/08/03/0906549106.full.pdf+html.

Astrocyte elevated gene-1 (AEG1), cloned and functionally characterized in 2005, modulates expression of genes associated with invasion, metastasis, chemoresistance, angiogenesis and senescence. It plays a major role in the progression and metastasis of numerous malignancies, including breast, prostate, liver, brain, CNS, and esophageal cancer, and may represent an effective strategy for disease prognosis and treatment. The sheer complexity of AEG1's interaction with several pathways implicated in malignancy, underscores the challenge of developing molecularly targeted anticancer therapeutics.

Stanford University scientists, using the concept of biologic networks to investigate how malignancies progress from a growing lump of unruly cells to an invasive, potentially deadly tumor, found that inhibiting beta-1 integrin (ITGB1, CD29) blocks the ability of cancer cells to grow and invade surrounding tissue. http://med.stanford.edu/news_releases/2009/june/khavari.html

Rosetta Genomics entered into a license and collaboration transaction with Prometheus Laboratories granting the latter with USA rights to 3 recently introduced microRNA-based cancer diagnostic tests.

According to results from a clinical trial (protocol ID: SCRI-CA-001; SCRI-CA-001; NCT00530192) released at the 2009 Meeting of the American Association for Cancer Research (AACR), molecular profiling of patients using the Caris Diagnostics' (Caris Dx) Target Now molecular profiling analysis identifies individual genetic profiles that often drive more informed and effective personalized treatment options.

Investigators at Kimmel Cancer Center, at Thomas Jefferson University (Philadelphia, PA), report that Mcl-1 is required for melanoma cell resistance to anoikis, a form of apoptosis induced by lack of adhesion or adhesion to an inappropriate matrix. BH3 mimetic compounds that target Mcl-1 may be effective for the treatment of melanoma in combination with agents that disrupt fibronectin-integrin signaling. (Mol Cancer Res. 7:549)

Investigators at Karolinska Institutet identified a new gene, Wrap53, that regulates the activity of p53 by producing an antisense RNA required for the production of sufficient quantities of p53 protein in the event of DNA damage.

SIAH1, an E3 ligase belonging to the human seven-in-absentia family of proteins, may represent a novel therapeutic target to stop tumor growth in Ras-mediated pancreatic cancer.  Generally, targeting the ras pathway has proven very challenging in drug development in oncology.

Newly identified gene (MACC1) is an independent prognostic indicator of the likelihood of colon cancer metastasis.

Researchers at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and the Charité-Universitäts Medizin Berlin, in Germany, using genome-wide expression analysis in primary and metastatic carcinoma, identified a gene, metastasis-associated in colon cancer 1 (MACC1), that is a high probability independent prognostic indicator of metastasis formation and metastasis-free survival of patients with colon cancer.  

The gene encoding the hepatocyte growth factor (HGF) receptor, MET, is a transcriptional target of MACC1.  MACC1 promotes proliferation, invasion and HGF-induced scattering of colon cancer cells in cell culture and tumor growth and metastasis in mouse models.  These phenotypes are lost in cells expressing MACC1 mutants lacking the SH3 domain or the proline-rich motif.  For clinical practice, MACC1 will be useful for the identification of patients with colorectal cancer with poor prognosis and is a promising new target for intervention in metastasis formation (Stein U, etal, Nat Med, Jan 2009;15(1):59-67).