Patented Biomarkers in Oncology

To date, Source MDx has developed Precision Profiles™ in Oncology for nine types of cancer including bladder, breast, cervical, colon, lung, melanoma, ovarian, pancreatic, and prostate. Precision Profiles™ in Oncology encompass over 1,000 technically validated gene assays that have been selected through extensive literature review, microarray analysis, in-house studies, as well as a general knowledge of genes known to be involved in specific cellular processes and pathways of interest. Collectively these target gene assays measure responses that are linked to specific cancers as well as responses that are associated with generalized cancer processes, including angiogenesis, apoptosis, tumor suppression, cell cycle, DNA repair, tumor invasion and progression. Equally important, Precision Profiles™ in Oncology reflect inflammation and immune-related responses through measurement of various cytokines, chemokines, growth factors and cell signaling molecules that have a demonstrated association with cancer.

Clinical Studies in Oncology

Over the last several years Source MDx has conducted independent prospective clinical studies for seven cancers including breast, cervical, colon, lung, melanoma, ovarian, and prostate. Exploratory clinical studies involving over 650 cancer patients and healthy normal control subjects, provided a broad overview of cancer specific, cancer general (tumorigenesis) and immune related gene expression responses across multiple cancers. Source MDx is currently conducting prospective validation studies involving over 2,000 cancer patients and control subjects across a variety of cancers, including breast, colon and prostate cancer in collaboration with the Dana Farber Cancer Center, lung cancer in collaboration with NYU Medical Center and ovarian cancer in collaboration with Massachusetts General Hospital and the Dana Farber Cancer Center. Additional pilot studies are ongoing in bladder cancer with the Dana Farber Cancer Center and in pancreatic cancer with the Translational Genomics Research Institute (TGEN). These Source MDx funded clinical studies along with ongoing trials in collaboration with pharmaceutical and diagnostic partners, provide access to several thousand cancer patient samples. Source MDx continues to independently support all clinical studies in oncology with the ongoing collection of blood bank, medically defined and subpopulation specific healthy normal control subject samples.

These clinical trials have resulted in a portfolio of diagnostic patents in oncology that claim to:

• Distinguish newly diagnosed patients from healthy normal subjects for early cancer detection.
• Predict survival of late–stage cancer patients to determine who may have a more aggressive form of cancer, for appropriate stratification of subjects in clinical trials.
• Characterize a common immune-related response across various types of cancer.

Link between Cancer and Inflammation

Source MDx's broad-based view and approach towards the molecular characterization of multiple cancers through unique (cancer-specific) and common (inflammation related and cancer general) sets of Precision Profiles™ is a deliberate contribution to the emerging integration of two distinct fields of research – cancer and inflammation. Our data provide the opportunity for re-exploration of old concepts, evaluation of more recent emerging hypotheses and perhaps formulation of new concepts linking cancer and chronic inflammation. A selection of relevant references reflecting the integration of knowledge, activity and current thinking within these two fields are provided below.

• Balkwill F et al. Cancer: an inflammatory link. Nature. 2004 Sep 23;431(7007):405-6.
• Bui JD et al. Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Curr Opin Immunol. 2007 Apr;19(2):203-8. Epub 2007 Feb 9.
• Coussens LM et al. Inflammation and cancer. Nature. 2002 Dec 19-26;420(6917):860-7.
• de Visser KE et al. De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell. 2005 May;7(5):411-23.
• de Visser KE et al. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006 Jan;6(1):24-37.
• de Visser KE et al. The interplay between innate and adaptive immunity regulates cancer development. Cancer Immunol Immunother. 2005 Nov;54(11):1143-52. Epub 2005 May 12.
• DeNardo DG et al. Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev. 2008 Mar;27(1):11-8.
• Karin M. The IkappaB kinase - a bridge between inflammation and cancer. Cell Res. 2008 Mar;18(3):334-42.
• Karin M et al. Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell. 2006 Feb 24;124(4):823-35.
• Karin M et al. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005 Oct;5(10):749-59.
• Lin WW et al. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 2007 May;117(5):1175-83.
• Lu H et al. Inflammation, a Key Event in Cancer Development. Mol Cancer Res. 2006 Apr;4(4):221-33.
• Mantovani A et al. Cancer-related inflammation. Nature. 2008 Jul 24;454(7203):436-44.
• Naugler WE et al. The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med. 2008 Mar;14(3):109-19. Epub 2008 Feb 7.
• Noonan DM et al. Inflammation, inflammatory cells and angiogenesis: decisions and indecisions. Cancer Metastasis Rev. 2008 Mar;27(1):31-40.
• Rüegg C. Leukocytes, inflammation, and angiogenesis in cancer: fatal attractions. J Leukoc Biol. 2006 Oct;80(4):682-4. Epub 2006 Jul 18.
• Tan TT et al. Humoral immunity, inflammation and cancer. Curr Opin Immunol. 2007 Apr;19(2):209-16. Epub 2007 Feb 2.
• Yu H et al. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007 Jan;7(1):41-51.