Cancer Research Guidelines

Last updated on: 05/17/2011

The purpose of cancer research is to reduce the mortality caused by this disease, to lower its frequency and severity by means of public health actions, and to improve patients' quality of life via more effective and less toxic treatments.

Research challenges

Priority actions to make progress in cancer research

Research Challenges

These were defined in the strategic orientation report from the cancer ITMO , AVIESAN and INCa and concern several areas:

Identify the causes of cancers

For half of cancers, the causes are well known, which makes it possible to conduct prevention policies, in particular against alcohol and tobacco.  But they remain to be characterised for cases where low risks or multiple causes are combined, making it difficult to identify them.  In addition, each individual has their own specific genetic characteristics, responsible for inequalities when faced with the risk of developing a cancer.  The efforts already made must continue in order to improve knowledge of genetic susceptibilities to certain cancers, and epidemiological knowledge to better identify the professional, environmental and behavioural risk factors.

Screen cancers at an early stage to avoid serious forms

The national system for organising screening for breast cancer and colorectal cancer makes early diagnosis possible. This makes prognosis more favourable and treatment easier.  INCa wishes to continue these surveys in order to devise screening strategies appropriate for other types of cancer.

Prevent relapse after treatment

Considerable progress has been made in treating cancers, but relapses are sometimes observed.  To prevent relapse, these treatments must be optimised, and this requires clinical trials involving a large number of patients.  The trials consist in comparing a "standard" treatment with a new combination of anti-cancer molecules for example, a new surgical or radiotherapy technique, or else a new management method. This will make it possible to determine the treatments that are most effective in preventing relapses.

Implement the progress made in fundamental research

Amongst other things, fundamental research makes it possible to increase our knowledge about how cells function, how tumors initiate, grow and disseminate in the body to give rise to metastases.  Transforming this new knowledge into medical progress for patients is currently a central concern.  This translational research has already led to considerable progress, including the development of "anti-angiogenic" molecules.  A tumor is capable of secreting molecules that stimulate the formation of new blood vessels (neo-angiogenesis), in order to favour and maintain its growth.  New drugs have been developed to prevent this from happening. They are called anti-angiogenic drugs and are used successfully in several types of cancer.

Develop genetic tests to improve personalisation of treatment

The technologies used to study genetic characteristics are not specific to cancer, and their capacities must be enhanced to better meet demand.  These modern gene analysis techniques make it possible to define precisely all the characteristics of a tumor and to consequently give the most appropriate treatment. This personalised approach optimises the response to treatment and reduces toxicity.  In addition, by determining the genetic characteristics of the tumour in individuals it is possible to adapt the treatment by not using molecules that would be partially or entirely ineffective for a specific patient.

Increase interfaces between research disciplines

Facilitation of exchange of knowledge and skills in the different fields of research is a vital step towards innovation.  Emphasis must be placed on grouping disciplines in joint research sites. In addition, fields essential to the fight against cancer such as imagery, radiotherapy and surgery, stand at the interface between several disciplines (physics, chemistry, mechanics, etc.) and have received limited research funding in France.  The initiatives launched by CEA for imagery and surgery foundations must be extended.

Priority actions to make progress in cancer research

The "Thematic Multi-Organisation Institute for Cancer (Cancer ITMO) has defined six priority actions in the short and medium term for cancer research.  These actions are determined in coherence with the recommendations of INCa's scientific advisory board and the priority actions of the Cancer Plan.

1) Support leading edge fields in cancer research

• Understand cancers to fight them more effectively.  Cancer mortality has dropped thanks to prevention, early diagnosis by means of simple tests and widespread use of digital imagery.  The progress made in reducing mortality is also due to the improvement in therapies. On the down side, the number of new cases of cancer rises every year, which justifies the reinforcement of research in order to understand the steps of cancerisation and to immplement more appropriate treatments.

Two difficulties have to be overcome: the appearance of cells resisting treatment, and the toxicity of medication for normal cells and tissue.  Treatment specificity must therefore be increased to spare healthy tissue.  To do this requires better knowledge about the functioning of healthy and cancerous cells, continuing the work begun some 30 years ago which have led to personalised targeted therapies (the target of the treatment is an inherent mechanism of the cell  and is prescribed according to the characteristics of each tumour).

• Simulate the body's natural defences. Knowledge of the immune system (the body's natural defences) have made it possible to develop treatments which stimulate these defences: immunotherapy. This vaccine-based approach is not yet a complete success, since studies show that cancer cells are capable of bypassing immune response mechanisms.  Multi-disciplinary research bringing together specialists in immunology and in cancer biology must be supported in order to develop an integrated approach and stimulate more active immune responses.

• Cancer study models. Researchers use different models to study cancer, some of which may seem far removed from the disease itself.  Yet it is by studying normal cells from rudimentary species such as worms and flies that researchers defined the concept of "cancer stem cells".  These cells are capable of turning into cancer cells and do not respond to conventional chemotherapy.  They are apparently responsible for cancer relapses. It is therefore possible to imagine new treatments that would have an impact on these stem cells.
• Develop the study of alterations in genes that cause cancers.  Genetics has made it possible to identify a large number of genes that play an important role in cancer, such as BRCA1 and 2 which predispose to breast cancer. These advances enable us to identify family members at a high risk of developing cancer and to characterise tumours better according to their genetic alterations.  The new techniques allow even more detailed and precise analyses, particularly of rare alterations.  These advances have led to the creation of major international programmes, such as the ICGC programme (International Cancer Genome Consortium) in which INCa is a participant.  This programme aims to define genetic alterations causing fifty very frequent cancers. The catalogue of genetic alterations thereby constituted will be made available to the entire scientific community.  Finally, one of the major challenges for cancer genetics will be to make the best possible use of the considerable amount of data that these techniques generate.

2) Improve exchanges between fundamental research and patient management

It is essential to translate the results of laboratory work into progress in patient mangement as quickly as possible.  These advances relate to diagnosis, choice of treatment, quality of life, etc.  This is the purpose of "translational" research, which must be developed in specific research centres.  It must put the priority on several areas:

• relations the tumour develops with its immediate environment;

• pharmacological mechanisms of new molecules in order to determine their toxicity and effectiveness as early as possible and develop new innovative treatments;

• research into "markers" indicating response or lack of response to targeted treatments.  A marker may be a molecule (protein, hormone, enzyme, antigen) produced normally by the body, the concentration of which increases in the event of cancer.  These markers are still rare; they only exist for certain cancers.  E.g. in the case of lung cancer, alteration of the EGFR gene is used to determine sensitivity to a specific targeted therapy.

3) Reduce inequalities in cancer care

Inequalities are observed in the areas of prevention, early diagnosis, access to quality treatments and survival. Collaboration between research teams in social sciences, public health and clinical research must be strengthened, not only to improve knowledge of social, economic and psychological factors leading to these inequalities, but also to take action to reduce them.

4) Bring together "biological" and clinical resources for tumours responsible for more than 70% of cancers

"Biological resources" are samples of cancerous or healthy tissue, blood, urine or other biological fluids that are taken with the patient's consent.  The collections are registered in INCa's national virtual tumor bank (TVN). The aim is to physically collect the collections, and large scale communication actions must be deployed towards patients so that they participate in major research projects (in particular the cohorts).

5) Develop research for effective treatments

This research is based on"clinical trials".  The trials consist in comparing a "standard" treatment with a new combination of anti-cancer molecules for example, a new surgical or radiotherapy technique, or else a new management method. The patient's consent must be obtained.

These trials are divided into four main phases, the first 2 of which are called the ‘early’ phases:

• Phase 1 is the first time the drug is administered to humans. In oncology, this phase only involves a small number of patients (typically 10 to 30) and aims to evaluate the safety of the drug as well as to determine the acceptable dosage without too much toxicity. The product is typically administered for a short period of time.

• Phase 2 is normally conducted on 50 to 100 patients. This is the first evaluation of the effectiveness of the drug on the disease, its optimal dosage and its effectiveness/tolerance ratio.

• If the results are positive, then the research will proceed with phase 3 trials, involving a larger number of patients.

• Phase 4 commences after market authorisation has been granted for the new drug and features a long-term evaluation on a large number of patients who are given the treatment.

The number of patients participating in the trials is still insufficient.  The objective is to enable 60% of children suffering from cancer to be included in a clinical trial, 40 % of patients suffering from a blood cancer, 10 % of those with solid tumor metastases and 5 % of patients aged over 75.
INCa wishes to reinforce clinical trials at the early stage by supporting dedicated research centres.

6) Make French research an international role model

The quality and dynamism of research teams is reflected by their scientific publications. France stands 4th in Europe in terms of scientific publications and the number of publications in the field of cancer is constantly growing.  Cancer research players must become more involved in international and European programmes. INCa and Cancer ITMO must also develop bilateral co-operation partnerships, particularly to facilitate clinical research.

INCa coordinates French participation in the International Cancer Genome Consortium (ICGC). The objective of this consortium, bringing together research teams from 22 countries, is to produce the list of genetic variations present in about fifty types of cancer.  Initially, the French teams are working on a form of liver cancer linked to alcohol and on a sub-type of breast cancer.  The results from all this data will be made available to the scientific community.

Finally, INCa has concluded an agreement with its American counterpart, the National Cancer Institute (NCI), to facilitate access to innovative cancer treatment molecules, both for French patients and researchers.  Clinical trials of innovative molecules are already under way in France.