MODIC

This strategy relies on a recent conceptual change of our understanding of cancer cell biology that stems from our discovery that transcription infidelity (TI) increases in cancer cells. Transcription is the process through which DNA transfers genetic information to messenger RNAs that leave the nucleus and are translated into proteins -cell functional arms-. Thus far, transcription was considered to produce absolutely faithful copies of DNA. We have shown however that this was not always the case and that TI increases in cancer. Because of this, a small portion of cancer mRNA has lost part of DNA information and produces abnormal proteins. A preliminary clinical essay shows that detection of abnormal TI protein (TIP) in blood samples provides a novel candidate marker of the recurrence of breast cancer in women undergoing follow-up. In addition, we have discovered that a subset of TIPs is encoded by mRNAs that have lost most of DNA information because of the removal of one base in the coding message. These aberrant proteins cause the appearance of low but detectable levels of antibodies in patients with cancer. Transcription infidelity antibodies (TIAB) levels in excess of those measured in normal subjects are detected in more than 90 % of currently tested patients with cancer. This small group (46 subjects) is constituted of patients with colon, lung, breast, ovary, uterus, head and neck and melanoma. In this group, 7 patients had early stage disease: (local tumor with no lymph node and no metastasis). Out of these 6 had detectable TIABs. Because the trial is small, the clinical significance of the results is preliminary and must be interpreted with caution. Nevertheless, our finding offers hopes that early stage cancer diagnosis using simple blood testing is foreseeable. However, current TIAB testing does not provide indication as to the localization of the tumor. Therefore the second goal of our program is to optimize the use of whole body in vivo molecular imaging with PET-CT to localize early stage tumors.