Benefits of cancer DNA testing

Last month we published a post on DNA testing for cancer predisposition and had an accompanying video on the types of DNA tests that are available for those people either afflicted with cancer or that have a family history of cancer.

This month we wanted to focus on those tests available to cancer patients, as mentioned in our video.

We’ll start by explaining how cancer patients can benefit from DNA testing.

First and probably of the most crucial value is the identification of a personalized treatment that would be more successful than just a standard, generic approach. This is referred to as a targeted therapy.

It has to be stated that in the tough drama with cancer there are many gambles involved in the fight for patient survival. DNA testing is one such gamble where actionable results can hopefully be obtained (results that will guide the treatment course). Luckily there is constant progress in the medical utility of cancer DNA testing so the gamble of any financial investment into such testing is getting smaller and better rewarded.

Our view at Merogenomics is that only taking a standard approach to cancer treatment should also be considered a gamble because DNA testing has already been used to increase patients’ outcomes in currently approved healthcare. There are already over a hundred approved personalized anti-cancer drugs. This field also continues to advance at an astronomical rate. Where we are now in terms of the molecular understanding of cancer (and how to take advantage of it) compared to not even a decade ago -shows that enormous leaps have been made. This has resulted in many new treatment options, and if the specific patient is paired with correct, personalized treatment, then there are extended chances of survival.

But what we need now is to see a dramatic surge in doctors employing this technology so we can quickly start learning how the best treatments should be selected for patients. Lack of doctor readiness to adopt DNA testing in their practice is becoming a real choke point for rapidly progressing personalized medicine. Doctors are keenly aware of the expanding use of DNA sequencing in medicine. But the majority of doctors have never been adequately prepared for the proper use of genetic information in their daily practice. Paradoxically, in a bid to protect their patients from harm, doctors are paralyzed without the proper approved guidance from local governing authorities - which usually takes a long time to materialize. The good news is that some doctors are rapidly trying to catch-up and learn about DNA testing on their own. By the way, this is often on their own personal time.

The second most acute benefit for the cancer patient is learning exactly how drugs should be effectively dosed or even if the drug could be potentially toxic to that individual. The difficulty with cancer is that it is a race against the available biological reserves of the patient and this affects their robustness. From talking with patients and their family members it is apparent that nothing aggravates them or stresses them more than waiting for results. The goal here is that DNA testing can remove a potentially costly gamble to patient health by introducing the extra understanding of how our body might process exact medications. In other words, DNA testing can reduce the trial-and-error phase of a patient’s response to a new drug. With cancer patients, whose biological reserves are under attack, trial-and-error with drugs can be costly to health.

This is referred to as pharmacogenetic testing and is probably the easiest, least risky and best method for doctors to become introduced to DNA testing benefits. This can really influence how the oncologist will deal with the standard treatments with which they are familiar. The biggest benefit is the potential to identify which drugs might be ineffective or harmful beforehand and thus allow doctors to consider more effective approaches to treating the patient.

This is referred to as pharmacogenetic testing and is probably the easiest, least risky and best method for doctors to become introduced to DNA testing benefits. This can really influence how the oncologist will deal with the standard treatments with which they are familiar. The biggest benefit is the potential to identify which drugs might be ineffective or harmful beforehand and thus allow doctors to consider more effective approaches to treating the patient.

Of course, there are other benefits such as helping towards the prognosis and informing other family members of a potential genetic predisposition, etc. But the most sought-after benefit is to increase the chances of a successful treatment for the patient and to speed up the process of treatment for the patient. These can both be achieved with DNA testing.

There are few ways of how DNA tests for cancer patients can be categorized.

Cancer DNA testing – getting more sophisticated

Probably the most important distinction to introduce to interested people is what the test will actually analyze. There are three different types of nucleic acids that can be all assessed for important information:

• The DNA that you were born with (referred to as germline) is expected to be the same in all of the cells in your body. This is the DNA you inherited from your parents

• The biopsy/tumour DNA. You can expect all cancers to occur due to mutations in your inherited DNA. Cancer DNA can be so mutated that you could almost think of it as the DNA of a different individual. These mutations in cancer DNA that have accumulated post birth (really, post fertilization), are referred to as somatic. This way you can differentiate between germline DNA mutations and somatic DNA mutations. The former you are born with, the latter you randomly collect through out life

• Cancer RNA. RNA is a very close relative of DNA. Chemically they are nearly identical. DNA acts as the store of information that is accessed to fish out pieces of code to be presented elsewhere for the cellular component’s manufacturing purposes or cellular behaviour management. Production of RNA is that fishing process. DNA can be copied into RNA, so the RNA now acts like a small blueprint that can be taken elsewhere, manipulated, and used as a map for building three-dimensional molecular robots. It is these robots’ work that provide the illusion of a cell being alive. If mutations in the DNA affect proper production of some of these molecular robots so their important function is affected, then such events can lead to cancer. How RNA mutations contribute to cancer we discussed in a previous month’s post

Now if you can appreciate how many different angles of molecularly looking at cancer are available you will see why cancer DNA testing can quickly get complicated. But all these pieces of information can in theory contribute towards an ideal targeted therapy selection.

Other ways to segregate the DNA tests are their costs, or complexity. These usually go hand-in-hand - so let us explain from simple to the more complicated approaches.

Cancer pharmacogenetic DNA test

The simplest and one of the cheapest tests available to cancer patients will be the previously mentioned pharmacogenetic test. This is also the test that is most likely to provide actionable results for the cancer patient: deciding how the patient should be treated, both in terms of drug selection and drug dosage. It is also one of the fastest tests from which to obtain results.

In our opinion, every single cancer patient should invest in this test if the drugs they will be treated with have established pharmacogenetic association (meaning that patient DNA mutations have established effect on how the drug of interest will impact the patient). If your chemotherapy is on the list, this test is worth your every penny for the potential grief it can save the patient if they were to be prescribed such tough treatments with limited or even toxic effects. In addition, you will be assessed for every single known medication with pharmacogenetic associations. Some of these patients could also end up with prescriptions to help deal with cancer and treatment related symptoms. Pretty much anyone can actually benefit from just pharmacogenetic testing (although we always promote full genome sequencing instead). Just be careful, there are many subpar DNA tests. This is especially important for minorities who are typically underrepresented both during the test development and test scope. Diving into the DNA test details is always worth it.

We previously covered topic of pharmacogentics if you need further detail.

We will also add, that a pharmacogenetic DNA test assesses your germline DNA, so in no way does it actually assess cancer related mutations.

Inherited cancer predisposition DNA tests

Another germline DNA test tests the cancer patient for inherited predisposition. This might seem odd, since testing a cancer patient for the knowledge of cancer predisposition looks like a test done too late. Apart from valuable benefits to other family members (who can then discover if they too inherited the same predisposition as the cancer patient), are there benefits to a cancer patient to learn they were genetically predisposed to cancer development?

It turns out that they can benefit. Certain treatments, called PARP inhibitors, are anti-cancer drugs used for patients with certain inherited cancer predisposition. We previously talked about this in a post dedicated to cancer mutations and cancer drug resistance.

Full genome DNA sequencing would cover capturing all of the germline DNA code in one go, so that would capture all the DNA information for the inherited cancer predisposition and pharmacogenetics. We discussed the topic of inherited cancer predisposition DNA tests in detail in last month’s post.

The following video from Merogenomics discusses at the time (around 2018) how frequently inherited cancer predisposition is discovered in cancer patients, what kind of mutations are expected to be found and what kind of response is called for.

Tumour DNA testing

The real deal and biggest hope for most significant actionable results is when the cancer biopsy itself is assessed for DNA mutations to discover what type of genetic modifications contributed to its existence. It is this critical information that is the most important to be used for the identification of a targeted therapy that will be specific to the cancer type with this specific DNA mutation pattern. Now you might think that where the cancer originates is not the driving factor of significance, but actually what mutations contributed to it in that specific section of the body. Cancers in different tissues can be arising due to same mutational pattern.

Biopsy DNA testing is not trivial though and very expensive. Much more so than looking at your germline DNA. It will run into multiple thousand dollars, and you could expect that a high-quality test will top the $10,000 mark. That is because the power of detection has to be massively magnified, as what is being attempted is to discover cancer mutations in a sea of normal germline DNA (from the healthy cells surrounding cancer cells). As we already pointed out, the goal is to figure out what DNA lesions contributed to the development of cancer, and hoping that based on that knowledge, a specific treatment can be selected that can take advantage of the altered system. But it is a gamble whether that desired connection between the DNA mutations and an associated treatment will be made.

However, if this connection can be made, it can have a profound impact. So profound that we at Merogenomics are a huge proponent of everyone having critical illness insurance in order to afford it. Cancer is the most likely disease to kill Canadians, and the majority of those who will be diagnosed will not have the opportunity to purchase tumour DNA testing, and in Canada to obtain such a comprehensive cancer genetic test covered by healthcare is very rare. Critical illness insurance which is paid out once diagnosed with cancer, can provide the investment needed for this expensive DNA test. Talk to any financial advisor about critical illness insurance if you need to learn more.

The tumour biopsy DNA testing will almost always be paired with your germline DNA testing to help understand the differences between those mutations that you were born with versus those that arose in your tumour.

It can also be paired with the analysis of RNA in the tumour. As we already mentioned above, RNA is an intermediate message between your DNA repository of information and biological molecules production. RNA can have its own issues that could promote cancer development. Most commonly due to how RNA is put together. Therefore just as there is a merit in analyzing RNA for heritable cancer predisposition, the same reasoning applies to the analysis of RNA in your cancer biopsy. For further background on RNA function check out our last post.

The amount of molecular information collected at that point is so vast that you need specialized computational methods and lots of computing power to interpret the information. There are not that many facilities in the world that are experts in this. This is where right selection of a company providing the test is so crucial.

Liquid biopsy

The final type of DNA testing technology we will mention, liquid biopsy, is still considered experimental - on par with where cancer DNA sequencing might have been viewed just a mere few years ago. Merogenomics is not yet affiliated with any companies offering such a service, but we are carefully monitoring the market at this moment. Nevertheless, we will introduce the concept as we expect this technology to yield important progress in fighting or preventing cancer, and we realized that we have not yet introduced the concept on our blog.

We are talking about monitoring DNA from cancer cells that are freely floating directly in our blood stream. This is equivalent to how non-invasive prenatal DNA tests (NIPT) work, which we already promote. Alternatively, it can also include monitoring the blood stream for presence of intact cancer cells. Together, these types of tests are referred to as a liquid biopsy.

What is amazing with such testing as liquid biopsy is that it can allow extremely early identification of the presence of cancer in a person, and as we already know from NIPT, this approach can be extremely sensitive in detection.

The potential utility of a liquid biopsy can be even more fantastical. It is feasible that it could be used to also directly monitor the tissue origin of cancer, through epigenetic markings on the cancer cells DNA (chemical information attached on top of the DNA).

The tricky bit with a liquid biopsy is that we need to know what to look for, as cancer presence is identified through specific cancer-related types of mutations in DNA. This means we need to know which DNA mutations to look for in order for detection to occur. We can take a random shot in the dark (certain cancer mutations can be observed more frequently than others, and we could aim for detection of those), or this type of information can be taken advantage for those patients who had their tumour biopsy sequenced. This is another huge advantage of assessing a tumour biopsy. The identified DNA code could be used to probe for the recurrence of cancer in the future!

If you know what cancer DNA mutations to look for (whether because we know a patient’s former cancer DNA mutations or because we are randomly assessing for selected mutations of choice), in theory you can discover presence of cancer growth dramatically earlier than clinical examination would typically reveal, meaning, we are catching the cancer presence at an early stage of development where it is usually the easiest to deal with. However, the test is still pricy, looking at even few hundred dollars per assessed single mutation. What is the efficacy of testing, or how often false results can be generated still needs further expansion in the use of this technology in medical practice. But the incoming data is looking very promising.

Another way you can use this technology is for screening for specific somatic cancer DNA mutations and even cancer predisposition germline mutations to understand a treatment approach, but the only justification for adopting such approach over the conventional methods mentioned above would have to be perhaps the speed of obtained results.

We are quite fascinated with this technology and we certainly will be coming back many times in the future to this topic and we expect to be distributor of such tests once we feel certain we have found the best provider.

The bottom line is that there are plenty of different ways how DNA sequencing technologies can be employed for the benefit of cancer patients, and even cancer survivors (with either liquid biopsy monitoring or germline investigation for heritable cancer predisposition to protect other family members or guide reproductive decisions). It is always worth your while to talk to your treating oncologist about the possibility of using DNA sequencing to guide treatment selection (although expect it to be an out-of-pocket expense), and in some cases, you should insist on using the DNA sequencing. Pharmacogenetic testing for the approved treatment that a patient is about to go through is truly worthwhile to potentially save oneself from lots of pain.

If you need Merogenomics assistance with getting access to some of the best quality medical DNA tests in our catalogue of tests we distribute (from some truly amazing DNA test providers), please do not hesitate to contact Merogenomics for cancer DNA testing guidance.

Whether any cancer patient ends up using DNA testing to improve their chances of healing, or sticks to traditional standard approaches without further insight from DNA sequencing, we wish all those affected, their families, and their treating oncologists (which are far more invested than you would ever know) the best of luck in what is always a scary and difficult journey.

This article has been produced by Merogenomics Inc. and edited by Jason Chouinard, B.Sc. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

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