Using Genetic Testing to Advance Cancer Care

Introduction

Genetic testing and analysis are revolutionizing health care, including cancer diagnosis and treatment. Probing a tumor’s genetic material can help doctors better understand, monitor, and treat their patients with a much more precise and individualized approach. To get there, scientists need to learn much more about how to interpret the genetics of cancer. Bioinformatics will be “fundamental to all cancer care and treatment going forward,” says Dr. Lynn Fink, PhD, Laboratory Director and Technical Director at the Australian company, XING Cancer Care.

XING Cancer Care is part of XING Technologies, a company dedicated to developing nanotechnology platforms for comprehensive genetic analysis for use in point-of-care diagnostics. Building on this mission, XING Cancer Care wants to work with clinicians to test tumors and provide them with critical genetic data. For instance, XING can provide information about a tumor’s alterations as well as clinical trials, based on the genetic profile. Currently, XING Cancer Care is focusing on a 1000 cancer gene panel to test for variants in tumors. In the future, XING Cancer Care envisions offering a whole array of technologies, including whole- transcriptome sequencing of a patient’s cancer and monitoring of disease during treatment and remission. “It will be very personal for patients,” says Fink, “And it can give them a really good understanding of their own tumor, their disease, and how they can best combat it in the future.”

iCommunity spoke with Dr. Lynn Fink about how bioinformatics can inform cancer care, how XING Cancer Care’s services compare to more traditional approaches, and why the company depends on Illumina products, the DRAGEN Bio-IT Platform and BaseSpace Sequence Hub, to do their work.

Lynn Fink, PhD is the Laboratory Director and Technical Director at XING Cancer Care.

Q: What is the focus and mission of XING Cancer Care?

Lynn Fink (LF): We We’re starting with a 1000 cancer gene panel, which is for cancer patients who have failed first-line treatment and are looking for other options. It’s about expanding the treatment possibilities for cancer patients. Once we start to build a business, we’re hoping to have a menu of items to support people through their treatment journey, including monitoring their disease. For example, if they intend to take a certain drug for their cancer, but their genetics suggest that they won’t respond very well to it, we can warn the oncologist that it may not be the best option. But that offering is still under development.

Q: Who are your customers? Are you only working with patients with certain types of cancer?

LF: We’re focusing just on solid tumors right now, like breast cancer, prostate cancer, and lung cancer, as opposed to blood cancers like leukemia, which we’re not doing yet. It can be for anyone in the world. We’re in Australia, so we’re hoping Australian patients will use us, but because we’re so closely placed to Southeast Asia, that’s a significant market for us as well.

Q: What is your role at the company?

LF: It seems to change every day. I was initially brought in to do business development, but because I have a background in cancer genomics and bioinformatics, I’ve been applying those skills to help get ISO15189 accreditation for our lab and also to set up the methodology for the cancer sample data analysis. My original title was Technical Director, which it still partly is. I’ve also taken on the role of Laboratory Director, which means I oversee all of the operations in our genetic testing lab. That includes management review meetings, setting up the bioinformatics, making sure that we meet all of our quality management thresholds. It’s more of an operational role, but I’m also heavily involved in clinical report generation.

Q: What role does bionformatics play in cancer care and treatment?

LF: Bioinformatics is fundamental to cancer care and treatment. The most comprehensive data we can get for a cancer genetics test is based on next-generation sequencing. The only way to make sense of that data is to do bioinformatics analysis.

Q: What services does your company currently provide?

LF: There are two aspects to XING. There’s XING Cancer Care, which is our accredited clinical pathology lab. Right now, all we’re offering is the 1000 gene cancer panel, which is called XGP1000. But the other side to our company is an R&D arm aimed at creating a medical device platform for rapid and portable testing at point of care that won’t require a laboratory or a trained person to run. It could be designed for a wide number of things. Cancer could be one application, or even coronavirus.

"Bioinformatics is fundamental to all cancer care and treatment going forward. The most comprehensive data we can get for a cancer genetics test is based on next-generation sequencing."

Q: How will the 1000 gene panel inform your customers?

LF: It’s a much broader panel than what most people offer. Most cancer gene testing is either a single gene or a very small number of genes, maybe four or five. Our panel captures a larger number of cancer-related genes. We have 63 genes that are known to be involved in almost every type of solid tumor, and the rest of the genes are ones that are thought to be involved. Many of those genes play a role in drug response, which means that when we’re ready, we can start offering pharmacogenomic information. We haven’t added that information to our report yet. That’s sort of a future-proofed test.

It’s a new paradigm in cancer treatment right now, because a lot of doctors aren’t prepared to deal with that information. Those who are will have a better understanding of the biology of a specific tumor. For example, breast cancers aren’t all identical. They all have slightly different biological origins and responses to treatment. If your doctor has genetic information about exactly what kind of tumor you have, they can better understand how to monitor and treat it, and maybe also have an idea of prognosis or when you might relapse.

Q: How does what you provide compare to traditional cancer care approaches?

LF: Maybe the best way to answer that question is to tell you the story of how XING was founded in the first place. There was a patient who was involved in a clinical trial that one of XING’s cofounders was involved in as well. The patient was diagnosed with myelodysplastic syndrome, which eventually led to leukemia. She received traditional treatment, which meant that her doctors prescribed the usual standard of care and threw four different types of cancer therapy at her. She failed all of them and became increasingly sick. She was eventually given a few months to live.

But within this clinical trial she also got some genetic testing, and they found a alteration that had never been seen in leukemia before. It was actually only seen in uveal melanoma. But there was a drug for that specific alteration, and she was able to access the drug, even though it wasn’t indicated in her disease. She was given that drug and literally three days later she was completely cured. Her cancer was gone. That never would have happened if she didn’t have that genetic testing.

Unfortunately, the sad side of the story is that she went on to die from the side effects of the treatments that she had received initially. If she had gotten testing in the first place and been given the drug, then she would have been cured immediately and had no side effects from all the chemo that didn’t actually work. That’s the strongest case for this kind of testing. Not everyone will have that response, but you definitely don’t want to miss the people that do have that response.

Q: How do you see your company's services fitting in with the more traditional approach?

LF: It’s going to be up to the doctor. Obviously, they’re the ones who are on the front lines and they’re experts, so they have a good understanding of whether the standard of care is the best approach initially. Right now this is a good supplement. If their patient isn’t responding and they’re getting worse, then doctors can order the second test and try to find something more targeted. But I think there will be a lot of doctors who choose this in the first place, and go right for the targeted cure.

Q: Can you describe the process your customers go through when using your services?

LF: We’ve only just been accredited two weeks ago, so we haven’t actually had any patients yet. But the plan is that we won’t actually interact directly with the patient. The patient will probably be referred to an oncologist and the oncologist is the one who will order testing for them.

When we receive that test request form and blood and tumor tissue samples, we will sequence them and look for alterations that are clinically significant to their cancer. Then the report will go back to the doctor who requested it and the patient will meet with them to discuss the results.

We want to support the patient throughout their treatment journey, so if they want follow-up testing while they’re in remission, or if they go into relapse, we will continue working with them. We’ll keep all their information, as long as they consent, and we will be able to do follow-up testing that’s personalized for them. So it’s not just a one-off. We don’t give them the report and walk away. We want to stay involved and help them through that journey.

"...[Illumina] gave me a bioinformatics pipeline in probably a tenth of the time, if not less, than it would have taken for me to set up something by myself."

Q: What bioinformatics products do you use?

LF: Primary and secondary data analysis right now is with Illumina. Data goes into BaseSpace Sequence Hub and we use DRAGEN apps and the Enrichment app to sequence the data, align it to a reference genome, and call variants in the tumor and blood sample, if one is provided. The final step is for us to interpret the variants that we find and generate the clinical report.

Q: Why did you choose Illumina products?

LF: They were already set up and very easy to use. I didn’t have to do any validation of the methods, just verification. It gave me a bioinformatics pipeline in probably a tenth of the time, if not less, than it would have taken for me to set up something by myself.

Q: Are there any other advantages that Illumina products offer?

LF: In pathology there are many regulatory requirements that you need to meet, especially for bioinformatics software. For example, data security. Anytime we use a third party, we have to do an external audit on them to make sure that they’re meeting quality standards.

Illumina has already taken care of all of that. They conform to the data security guidelines that we need. It’s a service that we can trust, and we trust their data security. If we had done that ourselves, we’d have had to go through all of that testing and work at huge cost and time expense to us. The software that Illumina provides is already verified and they conform to all the data regulations that we need. That made the decision very easy. We were able to get our product up and running as soon as possible.

Q: Which DRAGEN pipelines do you use?

LF: DRAGEN Somatic and DRAGEN Germline.

Q: What challenges did you face when developing a bioinformatics pipeline? How did DRAGEN pipelines and BaseSpace Sequence Hub help you address these challenges?

LF: We were initially implementing our own bioinformatics pipeline and there was just so much overhead because we had to document everything, validate everything, and figure out where to store the data. It was becoming really intractable and taking so much time. And then someone in our company asked, “Why don’t we just use BaseSpace?” Because everything was all set up there, all the information that we needed, all the apps that we needed, all the data security that we needed, we didn’t have to do anything. So it was a really easy decision just to outsource everything.

It was so cheap too. That was the other thing. We were paying a lot of money to do all of our own analysis because we’d run it all on a cloud platform and that was much more expensive than BaseSpace. So it was a cost decision as well.

"...everything was all set up there, all the information that we needed, all the apps that we needed, all the data security that we needed, we didn’t have to do anything. It was so cheap too."

Q: What are the advantages of next-generation sequencing for cancer detection that XING will soon be offering?

LF: With next-generation sequencing, because you’re not looking for a specific genetic alteration, you can find alterations that you’re not expecting, or that are rarer. For example, I mentioned that for cancer testing, a lot of people do a single gene or very small gene panels. Those are generally aimed at known hotspots. You might have heard of the BRAF V600 alteration, a very common one in melanoma. If you’re looking for that specific alteration, you can develop a test just for that. But if the patient has other alterations, that test will miss them. So, our next-gen panel could find other alterations that are interesting and informative, which may guide treatment, that you wouldn’t look for normally.

Q: What other next-generation sequencing services are in the pipeline for XING Cancer Care?

LF: The next thing we want to incorporate is RNA, because that can tell us about another facet of the tumor biology. The RNA is a snapshot of the actual biological activity in a tumor. It tells you about which pathways are active, which can tell you more about which treatment might be indicated.

You can also find fusion genes with RNA, which are not something that we can find easily with a DNA panel. A patient may just get DNA testing and find no alterations of interest. But the RNA testing could identify a fusion gene, which could have be a drug target, or explain more about the biology to indicate how the drugs might affect that patient.

"With next-generation sequencing, because you’re not looking for a specific genetic alteration, you can find alterations that you’re not expecting, or that are rarer. "

Q: What do you see is the future of cancer care?

LF: As our knowledge of cancer biology improves, I think we will end up doing whole-genome testing on everyone. The problem right now is that we don’t know how to interpret all of the information. We have to keep it limited right now to five genes or 1000 genes, because we don’t know what to say about variants that haven’t been reported or studied yet. Eventually we’ll get to that point where we’ll be doing whole-genome sequencing, whole-transcriptome sequencing, using multiple technologies, to inform a report. It will be very personal for patients and give them a really good understanding of their own tumor, their disease, and how they can best combat it in the future.

Learn more about the informatics solutions mentioned in this article:

DRAGEN Bio-IT Platform, www.illumina.com/dragen

BaseSpace Sequence Hub, www.illumina.com/basespace