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Disease Diagnostics and Therapeutics

Early Cancer Detection

Cervical cancer morality was reduced by 90% after the introduction of the Pap smear as a screening test followed by colposcopy. Why can we identify and treat cervical cancer early but not lung, colon and other cancers? The difference is the two-tier screening strategy with an initial non-invasive and cost-effective test administered in the primary care setting followed by a definitive 2nd-tier test, which would be performed on a small subset of patients identified by the initial test. For most cancers the 2nd-tier tests already exist (e.g. colonoscopy, LDCT); it is the 1st-tier test that is not available. The Backman Laboratory and a team of collaborators develops two-tier cancer screening technologies. Our team leverages field carcinogenesis as the biomarker source: despite being histologically normal, the majority of cells throughout an affected organ have genetic or epigenetic alterations. We also use chromatin packing alterations as a universal marker of carcinogenesis. These nanoscale chromatin alterations are below the resolution of conventional microscopy but are detectable via the nanoimaging platform (aka. nanocytology). Consequently, the risk of cancer can be assessed by the nanocytological analysis of cells from an easily accessible surrogate site without the need for actually targeting a tumor, thus avoiding the use of invasive diagnostic tests. Read more….

The Backman Laboratory develops nanocytology performed on cells swabbed from easily accessible surrogate sites as the first-tirer screening test for cancer. Clinical trials have been ongoing across the US. Nanocytology has shown the ability to identify patients with early neoplasia across seven malignancies including lung cancer (cells collected by a buccal swab), colon (rectal cells), pancreatic (duodenal cells), ovarian (endocervical cells), esophageal (upper esophageal swab), prostate (prognostication of aggressive vs. indolent cancers among patients with Gleason 6 score biopsies), and hepatocellular carcinoma (prognostication of future cancer).  Nanocytology has shown promise to become a platform technology to screen for a variety of cancers through the automated analysis of cells swabbed from these easily accessible surrogate sites, allowing doctors to detect cancer at its earliest – and most treatable – stage.

Collaborators: Prof. Hemant K. Roy, M.D. (Boston Medical Center)

Chromatin Protection Therapies

For many cancers progression-free survival, even with the most advanced chemo- or immuno-therapies, is measured in months. Even when a cancer undergoes remission, it frequently finds its way back, only this time having become resistant to treatment. The key culprit is the cancer cells’ ability to adapt and develop resistance to therapy. The Backman Laboratory is developing new strategies to reprogram global patterns of gene expression via the physico-chemical regulation of chromatin packing in order to edit cancer cells’ ‘software’ and thus deprive cancers from the very ability of developing resistance to drug therapies. As a result, cancer cells can no longer adapt and develop resistance to existing chemo- or immunotherapies. These chromatin protection therapeutics (CPT) leverages the power of macrogenomic engineering to regulate the global pattern of gene expression, without changing the genes themselves. Chromatin packing regulation is also being explored to address other diseases in which global transcriptional reprogramming and transcriptional plasticity play a role in shifting cell states including Alzheimer’s disease, atherosclerosis, as well as for regenerative medicine and stem cell technology applications.

 Collaborators: Prof. Igal Szleifer, Hemant K. Roy, M.D. (Boston Medical Center), Guillermo Ameer