Cancer, as Dr Scott Fields explains, is not one disease, but actually many diseases lumped under one category.
“Cancer is complex because even the same cancers don’t share all the same mutations, so it is much more difficult to treat than any other medical condition,” says the Oncology Strategic Business Unit Oncology Development head of the multinational pharmaceutical company Bayer.
He was speaking to the media during a workshop on Challenges and Opportunities of Drug Development in Oncology during the first Annual Pharmaceuticals Media Day held by Bayer at their Berlin, Germany, headquarters in December 2017.
Earlier that day, his colleague, executive vice-president and Oncology Strategic Business Unit head Robert LaCaze, had spoken about the company’s cancer portfolio.
Using the example of lung cancer, LaCaze notes that in the 1990s, a patient would have likely received a combination of radiation, surgery and chemotherapy, for treatment.
Today, a lung cancer patient is more likely to first receive some sort of genetic testing to determine what type of genetic mutation is driving their cancer, and that will then determine the treatment plan.
“As you think about the investment that is needed and the time that it takes to do our research and development to get drugs to patients, you really have to be forward-looking almost a decade out.
“Today, the targeted therapies are really the mainstay of many cancer treatments, as well as the newer agents with the immuno-oncology approach,” he says.
In terms of Bayer’s focus in oncology drugs, LaCaze shares: “We’re looking for compounds that truly do make a difference for patients, that are highly differentiated.
“And our research approach has been to try to be either first in class or best in class as we bring new drugs to the marketplace.”
To this effect, the pharmaceutical company is zooming in on four specific platforms in oncology.
The first and broadest area is in oncogenic signalling.
This involves targeting the various biological pathways that drive the development and progression of cancer, for example, the survival-signalling pathway that allows cancer cells to bypass the natural process of programmed cell death and the DNA repair pathway that is often more active in cancer cells, allowing them to survive cell-killing (cytotoxic) treatments.
The aim is to identify small molecule agents that can block these pathways so that cancer cells can be more easily killed off.
Says LaCaze: “We do have a nice research collaboration with the Broad Institute (of MIT and Harvard in the United States) to develop really important therapies that we are tying a biomarker to.
“We’re trying to ensure that we can identify the patients who can actually respond to and receive the benefits of the drug.”
A biomarker is a protein that can be used to monitor the effects of a particular drug.
The next area is in antibody-drug conjugates (ADCs).
“ADCs are the platform where you actually take maybe a cytotoxic (agent) or a drug, (and) you would actually link it to some sort of a target that is important for cancer.
“And then, by doing that, you can deliver that drug directly to the cancer cell,” he explains.
By doing so, it is hoped that the side effects of the drug on healthy cells can be minimised.
Utilising a similar concept are the targeted thorium conjugates (TTCs), which is a novel platform being developed by Bayer.
“This is actually a way to deliver radiation right into the tumour,” says LaCaze.
Where in ADCs, a drug is bound to an antibody that can latch onto the cancer cell, the TTCs instead have the radioactive thorium-227 element as the passenger on the antibody.
Thorium-227 emits alpha-radiation that penetrates a layer of about two to 10 cells deep, killing those cells by breaking their DNA strands.
The last area is in immuno-oncology.
LaCaze says that their aim is not to come up with more first-generation treatments to compete with those currently already on the market, but to develop the next generation of immunotherapies for cancer.
These treatments aim to further boost or restart the body’s own immune system in its fight against the cancer cells.
“If you look at the immuno-oncology space, it has made very good progress in the last five or six years, but yet, less than 30% of patients actually receive benefit from these compounds in terms of tumour reduction.
“So that means 70% of the patients need something else.”
He adds that even for the less than 30% of patients who initially responded to the immunotherapy, around 80% of them will require another treatment within a year as the cancer would have found a way – usually via mutation – to get around the treatment.