Personalised Medicine at a Glance: Stomach Cancer
For patients, policy makers and other non-medical professionals
This text was prepared by ESMO for the European Alliance for Personalised Medicine – March 2015
The aim of personalised cancer medicine is to give each patient the treatment that best suits his or her particular circumstances. Increasingly, this now includes identification of the specific molecular abnormalities that caused the cancer and that drive continued tumour growth.
Historically, stomach cancer has been very difficult to treat successfully. But we are now making good progress in tailoring surgery to the size and spread of the tumour at diagnosis and in selecting drug treatments according to the exact gene mutations of the tumour cells themselves. In this way, medicine is becoming both more personalised and more precise.
In Europe in 2012, there were around 140,000 new cases of stomach cancer. Although this disease is the sixth most common cancer, it is the fourth most frequent cause of cancer-related mortality and is responsible each year for more than 100,000 deaths.
With stomach cancer, a vital first step is to assess how deeply the cancer has invaded the lining and wall of the stomach. As with all tumours, the approach to therapy will also depend on whether the cancer has spread from the stomach to nearby lymph nodes and perhaps to sites elsewhere in the body. Distant spread of a tumour is termed metastasis.
If the stomach cancer is small and well-differentiated (ie it is made up of cells that retain many normal characteristics) the chances of spread are relatively low and surgical removal of the tumour and a margin of surrounding tissue may achieve cure.
Where the cancer has spread locally but has still not reached distant parts of the body, partial or complete removal of the stomach and nearby lymph nodes can achieve long-term survival in perhaps one in four patients. The chances are improved by giving chemotherapy before and after surgery (perioperative treatment) using cytotoxic drugs that kill rapidly dividing cells. The addition of radiotherapy following surgery is an option in some patients. But its overall value remains unclear.
When stomach cancer has become metastatic and potentially curative surgery is not possible, chemotherapy can prolong life but will not cure the disease. Moreover, it has adverse effects on many healthy cells (such as those in the bone marrow) which share with cancers the fact that they are rapidly dividing. So there is growing enthusiasm for more targeted forms of drug therapy that offer the promise of being both more effective and less toxic.
As with all cancers, stomach cancer is really not one disease but many – since a number of different gene mutations can cause cells to replicate out of control.
With several types of common cancer (notably breast, colon and lung cancer, and melanoma) our understanding of the precise gene defects that drive the tumour in an individual patient has led to personalised drug treatment using new agents that target specific molecular abnormalities. This is now becoming a reality in some patients with stomach cancer.
Around 10-15% of stomach cancer patients have tumours in which a particular gene mutation leads cells to produce too much of a protein that acts as a growth factor receptor on the cell surface. The specific protein is called human epidermal growth factor receptor 2 (HER-2). Overexpression of HER-2 leads to too much activation of pathways that signal the cell to divide, resulting in uncontrolled growth.
Before its role became clear in stomach cancer, scientists realised that many breast tumours were driven by HER-2. They therefore developed a biological drug (termed a monoclonal antibody) which specifically prevents growth signalling through the receptor. Once it had proved effective in HER-2 positive breast cancers, doctors began looking at other tumours which might share this molecular abnormality. Stomach cancer was one of them.
Clinical trials have now convincingly shown that in stomach cancer patients whose tumours overexpress HER-2, adding the anti-HER-2 drug trastuzumab to standard combination chemotherapy significantly improves survival duration. Combining this biological agent with cytotoxic drugs is now standard of care for patients with this type of metastatic stomach cancer. In an effort to help patients whose tumours do not have abnormal levels of HER-2, the potential for directing drugs at other molecular targets is being actively investigated.
Assessing the degree of risk posed by a stomach cancer at diagnosis is still the cornerstone of personalising treatment. This depends on the size of the primary tumour, and its degree of spread locally and to sites distant within the body. But taking tissue samples to establish the molecular characteristics of the tumour cells themselves is now also becoming important.
There are already at least six different treatment pathways that an individual patient with stomach cancer may follow. With our rapidly advancing understanding of the gene defects that underlie uncontrolled tumour growth, and parallel advances in molecular diagnostics, there will soon be many more.