Rising Cancer Rates in the UK

Cancer experts now believe that rising cancer rates mean 42% of Britons (1) or four in ten people in the UK will get the disease at some point in their lives (2). Macmillan Cancer found of the 585,000 people who died in the UK in 2008, 246,000 of them-42%-had been diagnosed with cancer at some point (1). Macmillan says the increase is mainly due to the UK’s ageing population and other factors such as increasing obesity, diet and exercise, and improved diagnosis (2). Dr Clare Gerada, chair of the Royal College of GPs said “If diagnosed early enough, cancers such as breast, skin and colon cancers are treatable, and many patients will go on to live long and healthy lives. Early diagnosis is vital, and this depends largely on patients presenting to their GPs as early as possible, and GPs having greater access to diagnostics” (1).

Matrix metalloproteinases (MMPs) are a family of highly homologous protein-degrading zinc dependent enzymes endopeptidases (3). Recently this family has been linked to tumour growth, progression and metastasis as well as dysregulated angiogenesis (4). As a result, these proteases represent important therapeutic and diagnostic targets for the treatment and detection of human cancers (4).

Breast Cancer

Breast cancer is the most common cancer in the UK. Around 50,000 people are diagnosed with breast cancer each year (5). The lifetime risk of developing breast cancer is 1 in 8 (5). One member of the MMPs family, MMP-9, shows elevated levels in tumour tissue as well as serum, plasma, and urine in patients with breast cancer (4). One of the major factors involved in remodeling process is matrix metalloproteinases (MMPs) such as MMP-13 that has been shown to degrade the native interstitial collagens in several tissues (6). In addition, MMP-9 levels decrease after treatment/therapy and more importantly, in all relapse cases there was a gradual increase in MMP-9 activity 1 to 8 months before clinical diagnosis of recurrence, consequently MMP-9 and MMP-13 may prove useful as prognostic indicators for breast cancer (4).

Pancreatic Cancer

In the UK approximately 8,000 people each year are diagnosed with pancreatic cancer (7). Pancreatic cancer is extremely difficult to diagnose in its early stages due to lack of specific symptoms and limitations of current diagnostic methods.  This may mean pancreatic cancer is more advanced when it is first found (8). Recently it has been shown that serum and tissue levels of MMP-9 are significantly elevated in patients suffering from pancreatic ductal adenocarcinoma compared to patients with chronic pancreatitis and/or healthy controls (4). Furthermore, active MMP-2 levels are higher in pancreatic juice of patients with cancer (100%) as compared with patients with chronic pancreatitis (2%) or normal controls (0%) (4).

Lung Cancer

Lung cancer is the deadliest type of cancer for both men and women, and is the second most common cancer in the UK, with more than 38,000 people diagnosed each year (9). Each year, more people die of lung cancer than breast, colon, and prostate cancers combined (9). Nearly 60% of people with lung cancer die within a year (10).  Recent findings have shown that plasma/serum levels of MMP-9 and TIMP-1 are up regulated in patients with stage III or IV lung cancer in comparison to those with non-malignant lung diseases (4).  MMP-7 levels have been shown to correlate inversely with overall response to chemotherapy and could prove useful as a prognostic biomarker predictive of response to adjuvant therapy (4).

Bladder Cancer

Each year nearly 10,000 people in the UK are diagnosed with bladder cancer (11). Studies have shown that urinary MMP-2 and MMP-9 levels correlate with presence of bladder cancer as well as stage and grade of disease. The stage of a cancer describes its size and whether it has spread and the grade gives an idea of how quickly the cancer may develop (11). Consequently MMP-2 and MMP-9 could assist in deciding on the most appropriate treatment for particular patients. Each urinary MMP species was detected at significantly higher in rates in urine from patients with cancer as compared with controls (4).

MMP-2, -9 and -14 are among the most studied MMPs as biomarkers for ovarian cancer. MMP-9 activity in tissue extracts was significantly increased in advanced ovarian cancers compared with benign tumours.  MMP-2, -9, -15 and -26 expression in tissue or serum have been positively correlated with Gleason score in prostate cancer.  Among these MMPs, the activities of plasma MMP-2 and -9 increased significantly in metastatic prostate cancer (4).

In conclusion, the MMP family of enzymes are displaying significant promise in the tumour diagnosis/tumour monitoring arena and these biomarkers could potentially be exploited to improve clinical outcome for cancer patients.

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(4) Roopali Roy, Jiang Yang, and Marsha A. Moses (2009) Matrix Metalloproteinases as novel biomarkers and potential therapeutic Targets in human Cancer. Journal of Clinical Oncology Volume 27, Number 31, pgs 5287-5296








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