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Cizzle has made novel findings around the nuclear DNA replication protein Ciz1, which have potential to offer new biomarkers and therapeutic targets for cancer.
Ciz1 promotes DNA replication and is involved in its organisation and control. Cizzle has generated data which shows that Ciz1 is altered in a wide range of common solid tumours, and that the degree of disruption correlates with disease stage.
Published evidence links Ciz1 with lung cancer, with breast cancer and other oestrogen responsive cancers, and with several paediatric cancers.
Lung cancer is the leading cause of cancer deaths worldwide among both men and women, with an incidence of over 1.6 million new cases annually and more than 1 million deaths annually. In the United States alone, over 200,000 people are diagnosed with lung cancer annually. Lung cancer is responsible for more deaths of cancer patients than breast, colon and prostate tumors combined.
Smoking is the leading risk factor for lung cancer, with 80% of all new lung cancer cases occurring in former smokers. Yet, more than 1 billion people around the world currently smoke tobacco. Even with successful smoking cessation, the risk of developing lung cancer remains high. In fact the proportion of never smoker-related lung cancers is increasing, although the causes or and risk factor(s) are unknown.
There are two main histological types of lung cancers: non-small cell lung cancer (NSCLC) (80.4%) and small cell lung cancer (SCLC) (16.8%). NSCLC includes squamous cell carcinoma, adenocarcinoma and large cell carcinoma, which account for approximately 35%, 27% and 10% of all lung cancer cases, respectively.
In contrast to other cancers, there has been little improvement in survival rates for lung cancer in the past 30 years, with only 5% of lung cancer patients surviving beyond ten years (Cancer Research UK). This is largely because the majority of lung cancer patients are diagnosed with advanced or metastatic disease and therefore not eligible for a curative surgical resection. Thus, there remains a major unmet clinical need for a biomarker that can detect lung cancer at an early stage, when the chance for a cure is highest.
b-variant Ciz1 Biomarker
Cizzle Biotech Limited is focused on addressing this unmet clinical need with its proprietary b-variant Ciz1 biomarker. B-variant Ciz1 is a novel Ciz1 variant that lacks a portion of a key functional domain. Expression of b-variant is restricted to tumour cells and selective inhibition of b-variant Ciz1 is sufficient to halt the growth of lung cancer cells both in vitro and in vivo, highlighting its role in tumorigenesis.
Remarkably, b-variant Ciz1 is detected in the plasma of patients with lung cancer. Even in early stage lung cancer patients, b-variant Ciz1 is robustly detected using just one µl of plasma. The presence of b-variant Ciz1 in patient plasma offers a readily accessible cancer-specific marker of early stage disease. In addition to early detection of lung cancer, Cizzle believes its b-variant Ciz1 biomarker will find further application in the management of lung cancer, for example as a surrogate marker for efficacy and in surveillance of recurrence. Its potential in the management of other types of cancer is under investigation. The characteristics of b-variant Ciz1 biomarker make it ideal for development as either a clinical laboratory assay or a point of care diagnostic test.
Cizzle Biotech Limited