Getting under the skin of cancer
Researchers in Toulouse are homing in on why some patients with dangerous skin cancers do not respond to cutting-edge immunotherapy treatment, and are exploring ways to overcome this resistance.
Globally, skin cancer is the fifth most common cancer for men and seventh for women. About 132,000 cases of melanoma are diagnosed each year, a quarter of which are metastatic cancers that spread.
In SA, Discovery Health Medical Scheme recently reported that melanomas were its fifth most common oncology claim in 2017, at an average cost of almost R39,000 a month. But some melanoma cases are more expensive: its second highest payout for a cancer claim was R1m, for a 68-year-old patient with melanoma.
SA is also grappling with the complexities of skin cancer and HIV, as untreated HIV suppresses the immune system and increases the risk of melanoma.
While metastatic melanoma survival rates have improved significantly since the advent of immunotherapy drugs that activate the immune system to fight cancer cells, prognosis nevertheless remains poor for a number of people, and many patients develop severe side effects.
Some immunotherapy drugs trigger the production of antibodies that block “checkpoints” that mistakenly send messages to the immune system’s T-cells and stop them from attacking melanoma. The drugs help restore the immune response against the melanoma cells.
“Before 2010 only 12% of patients diagnosed with metastatic melanoma were alive three years later; after the introduction of the immunotherapy drug Ipilimumab, survival rates improved to 20%,” says Nicolas Meyer, a dermatologist at Toulouse University Hospital. Hopes ran high that more effective drugs would quickly follow suit, but it was not to be.
“It was so difficult to improve the prognosis that the firms that developed drugs named this cancer ‘the drug killer’,” he says.
There have been some advances: second-generation immunotherapy drugs such as Nivolumab have improved survival rates, and a therapy that combines it with Ipilimumab has proved even more effective. Both drugs are made by BristolMyers Squibb.
Nivolumab targets the PD-1 protein on T-cells to boost the immune response to melanoma cells, while Ipilimumab blocks a different protein, called CTLA-4.
However, Meyer says 40% of patients do not respond to even combination therapy.
He is working with scientists at the Cancer Research Centre of Toulouse (CRCT) to crack this problem. Researchers discovered that blocking the cytokine TNF enhances the response to PD1- in mice with melanoma, and are probing whether the strategy is effective in humans too. They are also exploring the effects of TNF on lipids called sphingolipids, and how targeting them may overcome resistance immunotherapy.
The researchers are based at Toulouse Oncopole, a campus that houses scientists from the CRCT side by side with clinicians and patients from Toulouse Cancer Hospital.
The unique collaboration aims to accelerate research development so patients can benefit as quickly as possible from new discoveries in diagnosing and treating cancer, says CRCT director Gilles Favre.
The hospital, which opened in 2014, was designed to facilitate research.
For example, it has a pathology laboratory on site, which means tumour samples can be transported from surgery to researchers within a matter of minutes, he says.
The site also houses a cluster of companies focused on health innovation, in fields ranging from healthy ageing to medical devices. One such company is Pixience, which specialises in imaging devices.
It is using artificial intelligence to try and improve the diagnosis of skin cancer, and is developing a device that reliably gauges whether patients have benign moles or malignant melanomas. If successful, the device could ensure the most urgent cases are prioritised for an appointment with a dermatologist. Like many countries, France has a shortage of specialists, and patients typically wait months to see a dermatologist.
“Our aim is to have highquality screening available in pharmacies that will provide a severity grade for the lesion or mole and then refer the patient to the dermatologist,” says Pixience’s Alexandre Delalleau.
IT WAS SO DIFFICULT TO IMPROVE THE PROGNOSIS THAT THE COMPANIES THAT DEVELOPED DRUGS NAMED THIS CANCER ‘THE DRUG KILLER’