Oncology has seen some remarkable advances over the past few decades. Cancer is a difficult and complex enemy – there are actually over 200 types of this illness and they are constantly changing in response to the therapies used against them. Today there is a wide range of different types of cancer treatments, including chemotherapy, radiation therapy, targeted therapy, immunotherapy, bone marrow stem cells transplants, hormone therapy and surgery. Some of the more exciting developments we can see in the field of precision oncology.
Several of the oldest treatments, such as chemotherapy, are still used today but they come with major side effects. This is because they do not differentiate between healthy and cancerous cells in our body – and kill both.
Better understanding of cancer biology acquired through many decades of painstaking research have allowed to develop targeted therapies. This is where we find some of today’s most exciting developments in oncology, and the companies that work on these new cancer treatments. These targeted therapies use the precise information about cancer to attack only cancer cells while sparing healthy cells, thus increasing the success rate and reducing side effects.
Over the years, several types of targeted treatments have been developed, most of which aim at blocking the activity of proteins that help cancer to thrive. The human body develops around 20,000 proteins, and about 6001 of them are functionally important for various types of cancers. Because cancer cannot function without those proteins, blocking or removing them entirely is a good strategy to fight the disease.
Advanced antibody therapies: guiding the immune system to attack cancer cells
Cancer cells can be selectively targeted with antibodies, exploiting the subtle differences between the diseases and healthy cells. There are cancer treatments that use antibodies which are specially designed to bind only to the proteins on the surface of cancer cells rather than any other cells in our body. As in the case of ordinary antibodies, once such antibody finds its target (a matching cancerous protein), it disables its activity and signals the immune system to attack the intruder.
Antibody therapeutics represent the fastest growing class of drugs on the market. Even after 35 years since the approval of the first antibody treatment, they are the subject of intensive research.
The most significant developments in this field in recent years have been around the so-called bispecific antibodies and antibody drug conjugates. Bispecific antibodies can bind to not one but two different types of cells, for example a cancer cell at one end, and a defensive T-cell (that can destroy the cancer cell) on the other.
Antibody drug conjugates combine the selectivity of an antibody and the high toxicity of a drug to which they are fused. This way the treatment is delivered to cancer cells rather than healthy cells, which reduces side effects.
There are hundreds of types of different cancers in existence, and each of them has many different types proteins on the surface of their cells that can mutate very fast in order to escape current therapies. Nonetheless, with more than 200 bispecific antibody treatments in development, our chances are not hopeless in this fight. Recent examples include Genmab’s bispecific antibody currently in the late stage clinical trials for lymphoma, Johnson & Johnson’s recently approved bispecific drug addressing two separate drivers of lung cancer or antibody drug conjugate developed by Daiichi Sankyo in collaboration with AstraZeneca, approved for one of the types of breast cancer.
Protein degradation – killing the cancer cells from within
Our bodies constantly create and eliminate a huge number of proteins. The proteins that make our bodies do not stay there forever, they are consistently recycled once they reach the end of their lifetime. During this process proteins are first tagged for destruction with a marker called ubiquitin and then degraded within a sort of a waste bin structure called proteasome. This is called protein degradation.
Scientists have created a new type of treatment based on protein degradation. Several types of protein degraders are currently being investigated in clinical studies to see if they can be used to treat breast and prostate cancers, as well as lymphoma. There are also early stage trials to develop protein degradation mechanisms for melanoma, lung, colorectal, and pancreatic cancers. Recently this new class of drugs has been generating tremendous interest attracting both large pharma companies as well as smaller players.
The leaders in this field are several small and relatively young companies focusing exclusively on this area of research, such as Arvinas, Nurix and C4 Theraputics. They are working to develop degraders for many different types of cancer. Some of these cancers have previously been thought of as untreatable, while others are being currently addressed by various therapies, however not without problems such as drug resistance, mutations within the cancer cells and disease progression. Protein degraders could potentially overcome all those limitations: the aim is to develop cancer treatments that are able to degrade the proteins that are normally outside the reach of other drugs.
What’s on the horizon?
With ever growing scientific knowledge of how cancer cells function, there are many potential new treatments that could improve the current standards of care in the near future. The number of clinical trials initiations in oncology have roughly doubled in last 10 years, reaching a historic high-level of 1600 studies started in 2020. The progress in clinical trials leads to approval of tens of unique new treatments each year. Examples include highly targeted enzyme inhibitors, antibody immunotherapies, and cell therapies, where patient’s own immune cells are collected, modified in the laboratory and returned to the patient’s body to fight the cancerous cells. New classes of therapeutics such as protein degraders emerge regularly, adding to the toolbox of already approved treatments.
Our team applies its highly specialist expertise and thorough analysis to follow closely a wide range of ongoing oncology drug developments and target the companies that should benefit from the potential successes in this field.
Candriam supports PrecISion Medecine Institute in oncology (PRISM), which is a consortium comprising the Gustave-Roussy Institute, the Central Supelec engineering school, Paris Saclay University and INSERM. Its efforts are focused on molecular analysis to accurately detect the molecular mechanism that causes cancer to progress in each patient at risk of dying from cancer. That is what is known as cancer modelling and, if successful, it can save around 200,000 lives a year over the long term. Watch the interview of Professor Fabrice André – Directeur de la Recherche de Gustave Roussy, oncologue médical spécialiste du cancer du sein and Professeur de médecine à l’Université Paris-Saclay.
