Most of us are directly or indirectly impacted by cancer, the second leading cause of death worldwide. While the disease still claims many lives - almost nine million in 20151, important scientific advances over the past decades have translated into increased chances of survival.
However, the battle is far from won: experts are forecasting a 70% increase in the number of cancer cases over the next two decades, and by 2030, cancer is expected to cause 13 million deaths a year, a nearly 50% increase. Cancer occurs when human cells grow uncontrollably, forming tumors that can then spread from one part of the body to another. It is on the rise due to several factors, including bad eating habits and an aging world population; older people being more susceptible to various forms of cancer.
Cancer can strike everyone, no matter where they live, although it proves fatal more often in low- and middle-income regions that have fewer healthcare and screening options. And it doesn’t only impact the patient but also their loved ones.
“Right after we found out that my wife was pregnant, my father was diagnosed with pancreatic cancer,” remembers Rick Gregory, who spent 12 years as a cancer researcher at Sanofi Genzyme. “He was 70 and looking forward to living for a long time and spending time with his grandson. But unfortunately, my dad won’t get to see his grandson grow up and my son will not know his grandpa.
My father got to know that he has a grandson. That really contributed to him fighting and going through round after round of chemotherapy and surgery – you can see the power of having family as a driving force to bring yourself through this. As a cancer researcher, these are the sort of things you want to prolong. You want to put off families having to deal with this; you want grandfather and grandson to be together for a long time.”
Advancing cancer knowledge
For decades, standard cancer therapies included surgery, radiation or chemotherapy, or a combination, but as researchers learn more about human genetics, they have also developed a better understanding of how cancer works. That has made it possible to develop new medicines that are meant to target a specific cancer and stop it from spreading. In fact, more than 70% of recent survival gains in cancer are attributable to treatment advances including new medicines.2
From traditional to new therapies
The term “cancer” doesn’t mean a single disease – scientists today recognize hundreds of different cancers that affect humans.
This makes treatment even more challenging because cancer isn’t an external attacker like a virus. “Cancer is us, when our own cells start growing out of control,” said Joanne Lager, Head of Oncology Development at Sanofi. “So, unlike an infection, where you can find something that's different between the infection and the host, the cancer is part of the host.”
As a result, scientists are using new ways to treat cancer that enlist the body’s own immune system to help fight the complex dangers that lurk inside each tumor. “We now have a deep understanding of the biology of tumor cells,” said Laurent Debussche, Head of Sanofi’s Molecular Oncology Research Therapeutic Area, who noted that new technologies are allowing scientists to analyze “massive” amounts of genetic data about cancer.
Returning to a field where it has been an innovator in the past, Sanofi is once again making cancer research a high priority, investing in new technologies and treatments for this enormous unmet need and engaging a complete transformation of its oncology portfolio for the next five years. One area Sanofi is focused on is developing new ways to deliver medicines to tumors that would allow one treatment to engage the immune system in multiple ways.
“Cancers grow very fast and they change easily, they can mutate and develop resistance to therapies,” said Lager. “That’s why we need lots of different ways to attack the tumor and we need to think about ways to combine therapies.”
“Science is about being curious, and there are some times when you are so excited because you know something that no one else in the world knows,” added Gregory. “The idea that you can translate these understandings into therapeutics to help patients is really a driving force behind why we do this, why we are excited about it.”
The Complexity of Cancer
The fight against such a complicated foe requires a much deeper understanding of how cancer works and how it fools the body’s own immune system; a sophisticated defense mechanism whose role is to identify and destroy threats like infections or cancer.
One of the main players of this natural defense mechanism is the T Cell, a type of white blood cell. When T Cells find a tumor, they can latch onto the tumor and destroy it. However, to ensure T Cells don’t destroy normal cells, the body has developed a “checkpoint system.”
T Cells contain a protein known as PD-1 (programmed cell death protein 1) and normal cells contain a protein called PD-L1. The two proteins bind together and act as a safety mechanism or checkpoint to keep T Cells from destroying the cells our body needs. Some tumors, however, also produce a lot of PD-L1, which naturally fools the T Cells and prevents them from attacking the cancer.
Early clinical success of checkpoint inhibitors, such as anti-PD(L)1 and anti-CTLA4, resulted in renewed interest in applying immunotherapy to cancer care. Unfortunately, only a fraction of cancer patients benefit from checkpoint inhibitors with up to 80% of cancer patients not responding or responding poorly to checkpoint blockade. One of the central questions in clinical oncology as well as in research is how to overcome this resistance. Sanofi’s scientists are working on finding answers.
“At Sanofi we are very focused on understanding why certain cancer patients benefit from checkpoint inhibitors, as well as other immune therapies, and others do not,” explains Dmitri Wiederschain, Head of Immuno-Oncology Research Therapeutic Area. “To better understand this difference in clinical response, Sanofi has joined major public-private partnerships in both Europe (Innovative Medicines Initiative) and in the U.S. (Partnership for Acceleration of Cancer Therapeutics) to study patient samples from immunotherapy clinical trials in great molecular detail. Based on this knowledge, we are designing new immune therapies and proposing new combinations of existing drugs.
Learning from patients is the foundation of everything we do in immuno-oncology at Sanofi. For example, our scientists have discovered that one of the reasons why tumors are resisting immune checkpoint treatment is because they produce too much TGFb molecule that is well known to make the tumors invisible to the immune system. As a result, we are now conducting research on drugs that block TGFb. Another cornerstone of our strategy in immuno-oncology is the concept of multi-targeting. We are aiming to design therapies that can simultaneously target several different ways of re-activating our immune defences against the tumor. We hope that these new drugs will help our immune system attack the tumor from every angle.”
Sanofi’s Renewed Commitment to Cancer Research
We are currently investing in three main areas of oncology research and development:
- Immunotherapy, which includes checkpoint inhibitors in order to determine whether they can make the body’s immune system more effective against the disease.
- Advances in genetic knowledge to better understand the subtle differences among related cancers so they can be treated in different and more effective ways. For example, 20 years ago cancer researchers considered lung cancer to be a single disease – and treated it that way. Genetics makes it possible to identify unique “biomarkers” on lung cancer cells, and one disease is now understood to be several different cancers. This understanding may lead to identifying several targeted therapies.
- The central role of sexual hormones in breast and prostate cancers. Researchers now understand that novel ways of targeting sexual hormone receptors can bring new therapies for breast and prostate cancers. For instance, in metastatic breast cancer, drugs named Selective Estrogen Receptor Degraders are bringing novel therapy for one of the deadliest forms of breast cancer. In addition to our own research, we are collaborating with other companies with expertise in cancer, like Regeneron in immuno-oncology.
- http://www.who.int/news-room/fact-sheets/detail/cancer, last accessed Aug. 2018
- QuintilesIMS, ARK R&D Intelligence, February 2017; WHO Cancer Database, March 2017; QuintilesIMS, March 2017; IQVIA, ARK R&D Intelligence, February 2017; IQVIA Institute for Human Data Science, March 2017