Clinical trials have enabled major discoveries to be made in cancer treatment. Although it is likely that these treatments will only be available in several years time, the future is bright.
Apr 07, 2015
Researchers from the University of Geneva (UNIGE) have discovered the technique used by mice to avoid other mice with an illness. The rodents can perceive the smell of the illness with their vomeronasal organ, present in many mammals but virtually inactive in humans. This breakthrough could lead to the development of artificial noses used to detect certain diseases such as cancer much earlier.
Sep 03, 2014
"L'Illustré" followed a patient who volunteered for a clinical trial on a new immunotherapy. Read the article (french)
"You have just a few months to live, a year at best.” So many patients suffering from advanced cancer are still handed this terrible sentence. But soon it may be replaced by a more optimistic message. Discoveries made during clinical trials have revealed excellent prospects in terms of the treatment of this disease. Patients who have taken part in such trials have responded well to new therapies (see Yi Zuo’s account opposite).
“Some advances are so impressive that I feel we have every right to be enthusiastic about them, said a delighted Olivier Michielin, oncologist at the Lausanne University Hospital (CHUV), on his return from the annual meeting of the American Society of Clinical Oncology in Chicago in June 2013. Everyone I met there was so optimistic.”
Nevertheless, we will have to wait several years before these treatments are granted marketing authorisation. Before being administered to patients in a clinical context, a drug must first go through several validation phases (see: “The birth of a drug”)
If these potential treatments are approved within the next few years, they will join the list of major developments made in the treatment of cancerous tumours. The therapeutic arsenal to which physicians have access is constantly growing; this makes it possible for them to tailor treatments to their patients’ specific needs, an approach which can already be observed in the field. “The way in which we manage cancer care has changed considerably over the past few years, from diagnosis through to choices of therapy, highlights Roger Stupp, director of the Oncology Department at University Hospital Zurich. There isn’t just one approach: it is often by combining different strategies that significant progress is made.”
For the moment, surgical removal of the tumour remains an indispensable part of treatment for the vast majority of patients. “When an operable tumour is removed, cancer cells can remain and could lead to a relapse, explains Professor Stupp. These new approaches give us hope of one day eradicating the disease for good.”
Mar 16, 2014
The special feature in the first issue of In Vivo investigated the promising combination
of the Yervoy and Nivolumab molecules in fighting cancer. But the hype died down at the end of January, when US
pharmaceutical laboratory Bristol-Myers Squibb announced its intention to extend testing before releasing its product onto the market. This sign of caution also caused the lab’s share price to drop. Using immunotherapy to fight cancer was nevertheless voted “Breakthrough of the Year” in 2013 by the prestigious Science magazine.
Immunotherapy involves using a variety of strategies to boost the patient’s immune system. “We are finally seeing sound results, says Roger Stupp. This approach still mainly concerns very advanced cancers, but should eventually prove useful in the treatment of intermediate-stage cancers.”
The first of these strategies is aimed at directly stimulating the immune response. This is the role of Yervoy, used to treat melanoma (a very aggressive form of skin cancer). This immunotherapy drug was the first to be approved by the US Food and Drug Administration (FDA) in 2011, and is also available in Switzerland.
A second strategy is to block the action of certain proteins found on the surface of cancer cells. These proteins inhibit the defensive activity of the white blood cells, known as the soldiers of the immune system. The molecule Nivolumab, which is still in the testing stages in the USA, works in this way and was found to reduce tumour size in one third of patients whose melanoma did not respond to prior treatment. This is a strategy that oncologist Olivier Michielin believes could work in a large variety of cancers.
A combination of these two approaches can produce even more spectacular results: in a recent clinical trial, sponsored by the American pharmaceutical company Bristol-Myers Squibb, which combined the use of Yervoy and Nivolumab, tumours shrank by 80% in over half of the 53 participants with metastatic melanoma.
Training the white blood cells – Therapeutic vaccination is another approach used in immunotherapy. Provenge, approved by the FDA in 2010 for the treatment of prostate cancer, falls into this category. It is now available on the American and European market, but is not currently approved for sale in Switzerland. The objective is to “train” lymphocytes (a type of white blood cell) to recognise cancer cells by putting them in vitro with antigens extracted from the patient’s tumour. Unlike conventional vaccines against influenza or polio, this type of vaccine has no preventive purpose but is administered once the cancer has been diagnosed.
George Coukos, currently head of the Oncology Department at the Lausanne University Hospital (UNIL-CHUV), led studies into the development of a vaccine against ovarian cancer in the framework of his research at the University of Pennsylvania, which now works in partnership with Lausanne. When combined with Avastin (see point 2, Targeted drugs), immune therapy was found to stabilise progression of the disease in patients with advanced cancer. According to Professor Coukos, this treatment could be made available to Swiss patients within the next two years.
Another promising experimental vaccine, developed to treat brain cancer, has been submitted for approval to Swissmedic, the Swiss Agency for Therapeutic Products. “We have been able to develop a vaccine by identifying the molecules present on the surface of tumours”, explains Pierre-Yves Dietrich. In recognition of his discoveries, the director of the Centre of Oncology at Geneva University Hospitals (HUG) was awarded the inaugural Annual Cancer Researcher of the Year Award by the American organisation Gateway for Cancer Research.
“A handful of treatments have already been put on the market, but the majority of them are only accessible at the moment through clinical trials,” notes Roger Stupp. “Swiss patients should get information on this treatment and ask their physician whether participating in a trial could help them in their fight against cancer.”
Towards gene therapy – Finally, gene therapy is the most ambitious approach. This involves adding a specific gene from the cancerous tumour to white blood cells extracted from the patient’s body. A spectacular case was reported in a study published in “Science Translational Medicine” in March 2013: the lightning cure by gene therapy of five patients suffering from leukaemia, with the most rapid cure taking only eight days. But this approach, used by researchers at the Memorial Sloan-Kettering Cancer Center (New York) is still in its experimental stage and, for the moment, the European Union has only authorised a single gene therapy, used to treat a rare genetic disease not related to cancer (lipoprotein lipase deficiency).
There are cancers and cancers. Once classified according to organs, tumours are now identified according to their biochemical modes of action or, in other words, the way in which cells react to other cells. Personalised medicine, the aim of which is to recognise each type of cancer and to attack it in a selective manner, is playing an increasingly important role in therapies. “Revolutionary results have been obtained with Glivec, one of the first targeted drugs,” points out Martin Fey, director of the Department of Medical Oncology, Inselspital, Bern University Hospital. “This treatment can cure chronic myeloid leukaemia, a disease that used to be incurable.” Among the better-known targeted drugs are Herceptin, for certain breast cancers (authorised in Switzerland since 1999), and Avastin (authorised since 2004), which inhibits the vascularisation that nourishes the growth of tumours.
These drugs act on precise molecular targets, unlike conventional chemotherapy treatment that attacks healthy tissue at the same time. “Some tumours, which are activated by DNA mutations, may be identified by genetic analysis,” explains George Coukos. “It is thus possible to identify a large number of new targets for targeted therapies that operate by blocking the defects generated by mutation. Some results are spectacular.” Before drugs can be used in therapy, diagnostic tests are conducted to ensure that the tumour is of the type that will react to the medication. Targeted drugs developed over the past fifteen or so years for use in oncology constitute new weapons in the arsenal available to physicians. Moreover, physicians sometimes use these strategies in combination with other approaches: surgery, chemotherapy, radiotherapy. This is another way of making the treatment for each patient more personalised.
Chemotherapy destroys cancerous tissues using powerful molecules, but it may also damage healthy tissue. New techniques developed in nanomedicine are aimed at using this type of therapy in a more selective way.
One ambitious idea which is currently being developed in research laboratories involves encapsulating chemotherapy molecules in a nanobox comprising a fatty membrane and onto which it is possible to attach proteins that are able to bind to cancer cells. The box is then “swallowed” by the tumour and delivers the chemical agent into the cancer cell – a microscopic Trojan horse.
The first FDA-approved nanodrugs, such as Abraxane or Doxil, work in a simpler way. Doxil, which is marketed in Switzerland, accumulates naturally in tumour tissue since the nanoboxes are exactly the right size to pass through the porous walls of the blood vessels leading to the tumours.
With other more conventional techniques drugs can be injected directly into the tumour. Francis Munier of the Jules Gonin Eye Hospital (Lausanne) has developed a method for treating children with advanced retinoblastoma (cancer of the retina). This procedure, which is practised in Switzerland, consists in the intravitreal injection of chemotherapeutic agents without risk of tumour spread, thanks to a fine needle cooled to -70°C. The eye was conserved in 20 cases out of 23, with no recurrences two years after the procedure.
Some predicted the decline of radiotherapy – but they were wrong. The use of radiotherapy dates back to the 19th century and has seen tremendous progress over the last few years: highly-targeted X-ray doses can now reach cancer cells with increasing precision, thereby avoiding damage to adjacent healthy tissue.
Generally speaking, progress in radiation therapy is inextricably linked to advances in imaging (scanners, MRI, PET), according to Stephan Bodis, expert in radiation oncology at the Cantonal Hospital Aarau. These devices provide highly refined images making it possible to target very precise areas of the body. “In certain cases, a single radiation dose in a very small volume may be sufficient to destroy the tumour.” This technique, known as stereotactic radiotherapy or radiosurgery, requires high-precision equipment such as the gamma knife system.
The potential of radiotherapy can be further enhanced through new approaches, including flash
radiation therapy. “This innovation is based on a very intense and extremely rapid radiation technique,” explains Jean Bourhis, head of the Radiation Oncology Department at the University Hospital of Lausanne (CHUV), where this autumn he will start conducting the first programme in the world to test this approach. “The radiation dose currently delivered in five minutes will be delivered in 0.1 second.”
The first tests will concern only shallow tumours, more specifically head and neck tumours. “In the long term, flash radiation therapy will likely be used for all types of cancer,” predicts Professor Bourhis. “It has the advantage of minimising inflammation of adjacent healthy tissue, enabling us to use higher doses of radiation. It could therefore be used to treat the most resistant cancers.” ⁄
Immunotherapy boosts the immune system so that it can fight cancer more efficiently.
The exact type of cancer is identified so that an appropriate drug can be used.
Active molecules are enclosed in nano boxes that have the advantage of accumulating only in the tumor.
The chemotherapeutic agents thus attack the cancer cells but leave healthy tissue unharmed.
by focussing radiation
beams on the cancer
cells. Radiation destroys the tumour but preserves surrounding tissue.