Effective and affordable cancer treatments are one step nearer

By European Alliance for Personalised Medicine Executive Director Denis Horgan

Scientists are getting very excited about immuno-oncology (I-O) which its proponents say will revolutionize cancer care. A new class of drug has arrived that is designed to encourage the body’s own immune system to attack malignant cells. 

The World Health Organization has predicted that the number of people dying from cancer will rise from 8.2 million in 2012 to 14.6m in 2035, yet these treatments are already coming up with the goods even in advanced melanoma and lung cancer.

Certainly, there will need to be a massive amount of development for some time but the dream is to eventually translate these cutting-edge immunotherapies into everyday, affordable treatment for patients with cancer.

There is certainly a lot of optimism around and these drugs have even been hailed in some quarters as the beginning of the end of cancer. And with nearly 300 clinical trials of immunotherapies happening right   now in the US, there are clear indications that pharmaceutical companies have a huge amount of faith in immuno-oncology.

New knowledge of the disease gained in recent times can account for advances in I-O – researchers discovered viral origins in certain forms of cancer and this, in turn, led to the idea of harnessing an individual’s immune system to attack cancerous cells.

This eventually brought about up-to-the-minute cancer vaccines, both as prophylactic treatment and as therapy, with three currently available in the US and several other vaccines being developed as you read this. It’s been a paradigm shift: Back in the late 1990s-early 2000s, cancer was thought to be a disease of genetic origins, with specific characteristics including the ability to promote invasion and metastasis. But this failed to take into account the dynamic nature of the interaction of the tumor with normal cells in surrounding tissue as well as the immune system.

The discovery of how human immune systems help tumour cells proliferate while avoiding detection has produced great leaps in immune-based cancer targeting and led to scientists understanding that immunotherapies could aid long-term tumour control or even eliminate them totally. Today’s immune therapies stimulate the immune system to get to work and the proteins being targeted are not organ-specific, leading to use in multiple tumour types. But the problem has always been keeping up a persistent memory response in antibodies.

The new I-O agents get around this, which increases the chances of successful combination immunotherapies. Several of these therapies are undergoing clinical trials and the results have brought reason for optimism. One of the major challenges in I-O is identifying the target population for each treatment in order to achieve the maximum results. Scientists are currently trying to identify potential biomarkers but further hurdles to overcome include determining the sequence of therapies as well as the duration of treatment.

The use of genetics and biomarkers to target the patient group that will benefit from a particular immunotherapy has its mirror image in personalised medicine, which has the goal of giving the right treatment to the right patient at the right time, and one clinical trial (of two combined drugs) has produced a response rate of more than 50% in patients with advanced melanoma. It was initially feared that these immunotherapies would only be able to treat melanoma, but that is not the case.

They have managed to shrink and, in some cases, eliminate tumours even in patients with advanced liver cancer. It has also been discovered that patients with high levels of a biomarker known as PD-L1 in their tumour respond much better than others. A recent study of lung cancer patients showed that immunotherapy was much more effective in PD-L1 positive patients, and reduced their risk of dying by 60% compared to chemotherapy.

Personalised medicine at its best. Meanwhile, pharmaceutical groups developing checkpoint inhibitors are working on companion tests to   predict which patients will respond but there is still a way to go. At the moment, plenty of patients who test negative still benefit from the medicines while the reverse is also true. In future it is expected that scientists will use cancer-cell DNA to determine the best approach for an individual patient. This is becoming faster and less expensive all the time and, as with all forms of personalised medicine, there is a need to understand which patients will benefit most from these new drugs.

Members of the Brussels-based European Alliance for Personalised Medicine believe that, further down the line, immunotherapies are likely to be best used as part of a combined approach.

This methodology will harness the body’s immune system in order to destroy cancer cells and attack them directly with the targeted drugs. On the down side, in the same way that other new ‘wonder’ medicines have come onto the market down the years with a high price tag, the drugs are hugely expensive at the moment. However, as more are developed, the purchase price should start to fall through competitive market forces. The very good news is that it appears that once the immune system has been trained to recognize cancer cells as ones to attack, a long-lasting ‘memory’ keeps the immune system doing its job even as the cancer mutates.

The probability is that, in the not-too-distant future, immuno-oncology treatments will destroy tumours completely in some patients, while others will be able to live with cancer as a chronic disease. In either scenario, this represents a giant leap in the bid to conquer cancer. No wonder the scientists are excited.

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