VolitionRx – Decoding the DNA of cancer 

A possible breakthrough in the NGS gridlock?

Isolating tumor-derived ctDNA from otherwise healthy cell-free DNA (cfDNA) circulating in the blood has been likened to finding a ‘needle in a haystack’ (ctDNA makes up less than 10% of a patient’s cfDNA and often less than 0.1% in early-stage cases). Available tests are generally not sophisticated enough to isolate ctDNA chemically, requiring complex, time-consuming and thereby expensive (c $1,000/test) DNA sequencing and computer algorithms (to map the entire genome to identify DNA aberrations). Volition is developing a simpler, quicker and more cost-effective solution with its first-of-its-kind liquid biopsy method using a proprietary CTCF-ChIP/qPCR method that allows for physical isolation of a class of ctDNA from cfDNA, thereby removing the need for sequencing. We discuss Volition’s underlying CTCF-based approach in detail but the general theory is that CTCF (a transcription factor) binds to different sites on tumor-derived DNA versus healthy DNA, making these potential cancer biomarkers. Volition’s CTCF-ChIP technology allows it to physically isolate these DNA-bound CTCF, which can then be tested for cancer using a simple polymerase chain reaction (PCR) test.

Early proof-of-concept data signal sizable potential

Volition has tested this new methodology using 10 quantitative PCR (qPCR) assays based on a leukemia model with good results – 74% sensitivity/96% specificity for leukemia using a 2-qPCR assay. Interestingly, some of the assays were also able to detect solid cancers (such as colorectal cancer) with high accuracy. This is despite the panels not being optimised for these cancers. More interestingly, these assays were able to spot 44% and 33% of stage I and stage II cancers, a key indicator in our opinion, supporting their pitch as effective early-stage cancer screens. We caveat that these data are preliminary and extensive clinical work is required to validate initial findings. Volition is working towards refining these tests and developing specific biomarkers for other solid cancers (CRC-specific assays are expected by Q124). Although early in its development journey, in our view the building blocks are in place for this technology to evolve as a potential disrupter in the space.

Early cancer screens in need of new blood

The growing burden of cancer and its impact on patients and healthcare systems alike needs no introduction. Cancer is the second-largest cause of mortality globally after cardiovascular diseases, accounting for one in every six deaths. In the US alone, it is estimated that over 600,000 people will succumb to cancer in 2023. According to the American Cancer Society, one in two men and one in three women will develop cancer during their lifetime. 

While these figures are disheartening, advancements in medical science have meant that nine out of 10 patients live five years or longer if their cancer is detected early. Studies suggest that cancer-related deaths can come down by at least 15% if detected before metastasis/stage IV. Yet close to 50% of cancers are only diagnosed at an advanced stage (stages III and IV) and only four cancer types currently have screening tests recommended by the United States Preventive Services Task Force. These include breast cancer – mammography; lung cancer – low-dose computed tomography (CT) scans; colorectal cancer – colonoscopy; and cervical cancer – pap test/human papillomavirus testing. In addition, a fifth screening test for prostate cancer – serum prostate specific antigen testing – is available but is not openly recommended due to low specificity. In Europe, the list is even smaller with only colorectal, breast and cervical cancer having approved cancer screening programs. While these cancers represent the most common cancer types (c 50% of all cancer cases), it is also telling of the fact that an equally large population remains underserved with no recommended early cancer screening tests. Moreover, available data indicate that only 14% of cancers are currently detected through a preventative screen. This highlights the significant unmet need in this space. Exhibit 1 captures the five-year survival rates for the most common cancers, when detected early versus at a late stage.

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Soo Romanoff

Managing Director – Head of Content, Healthcare

sromanoff@edisongroup.com 020 3077 5700