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Identifying Biomarkers Gives Doctors Known Targets to Treat Many Cancers

This blog was originally published by Cancer Treatments Centers of America on August 21, 2019, here.

Biomarkers
Doctors are increasingly relying on biomarkers, which help determine a patient’s overall health and/or the presence of disease. Learn what biomarkers are and why they are increasingly important in cancer care.

When faced with opposition, it’s beneficial to learn as much as possible about the opponent. A pitcher reads a scouting report before facing a lineup. An army consults intelligence before engaging the enemy in battle.

The same principles apply to the treatment of some cancers. When treating a tumor, it’s important for a doctor to know as much as possible about that cancer—specifically, what is driving the tumor’s growth.

To get the inside information on a tumor, doctors are increasingly relying on biomarkers, short for biological markers, measurable signs or substances in the body that may indicate a patient’s overall health and/or the presence or progression of disease.

The discovery of biomarkers in cancer drastically changed the course of cancer treatment. For decades, many cancers were treated similarly, with surgery, radiation therapy or chemotherapy. Identifying biomarkers in cancer cells has led to the development of new precision medicine drugs, such as targeted therapy and immunotherapy, designed to target specific features in cancer cells, potentially reducing the damage to healthy cells. “The routine use of a variety of biomarkers has substantially changed the way in which cancer medicine is practiced,” says Maurie Markman, MD, President of Medicine & Science at Cancer Treatment Centers of America® (CTCA), “from providing more accurate prognostic information to assisting in the prediction of specific therapeutic strategies that are more likely to result in a favorable outcome for an individual patient.”

What are biomarkers?

A biomarker is any measurable indicator of a person’s health. Blood pressure is a biomarker, as are body temperature, blood sugar and cholesterol measurements. In cancer, biomarkers also include proteins, hormones, gene aberrations, such as mutations or rearranged genes, and other molecules found in or on cancer cells. Cancer biomarkers may be found in routine blood, urine or stool tests. Others may require a biopsy and/or advanced genomic testing to uncover. “Genomics has made it so much easier to find gene mutations,” says Arturo Loaiza-Bonilla, MD, MSEd, FACP, Vice Chair for the CTCA® Department of Medical Oncology. “Now we may be able to target a mutation and potentially get the cancer to stop growing.”

Biomarkers play multiple roles in the treatment of diseases, such as cancer, including:

Diagnostic: Helping confirm the presence of disease, sometimes before symptoms develop

Prognostic: Helping forecast the progression and aggressiveness of the disease and the risk of recurrence

Predictive: Helping doctors identify how patients may respond to certain drugs

Biomarkers may play any or all these roles and more. Some biomarkers may be used to assess a patient’s risk of developing disease, the effectiveness of a treatment or whether a treatment is safe or toxic.

Common cancer biomarkers include:

  • BRCA1 and BRCA2 genes: Mutations in these genes may increase a woman’s risk of breast and ovarian cancer. In men, it may increase the risk of prostate cancer.
  • PSA: Prostate specific antigen may indicate prostate cancer. This biomarker may be used not just to diagnose the disease, but to measure its progression and how the treatment is performing.
  • HER2: Human epidermal growth factor receptor 2 is found in many cancers, especially breast cancer. The targeted therapy drug trastuzumab and other similar monoclonal antibodies may be a treatment option for patients with HER2-positive cancers.
  • BCR-ABL: This gene, known as the Philadelphia chromosome, is found in patients with chronic myelogenous leukemia. Presence of the gene may indicate the patient may respond well to treatment with a tyrosine kinase inhibitor drug such as imatinib.
  • PD-L1: Programmed death ligand 1 is the companion receptor to PD-1. It may indicate a cancer’s ability to evade the immune system. Immunotherapy drugs called checkpoint inhibitors may be an option to treat cancers high in PD-L1.
  • CA-125: High levels of cancer antigen-125 are found in many cancers as well as other diseases. Treatment options for cancers with CA-125 vary depending on where the cancer originated.
  • MSI-H: Microsatellite instability-high is a mutation in the DNA of cells found in many cancers, especially colorectal cancer. Checkpoint inhibitor drugs have been approved for cancers with MSI-H.

Difficult targets

Biomarkers don’t always tell the full story. Discovery of a biomarker that might indicate an increased cancer risk doesn’t mean a patient will get cancer. Not all cancers have identifiable biomarkers. And identifying a driving biomarker in a cancer does not necessarily lead to a treatment option. Some biomarkers for cancer have no corresponding targeted therapy or immunotherapy drug. For example:

  • TP53: Tumor protein 53 is a tumor suppressor gene designed to help stop cancer cells from growing. TP53 mutations are the most common found in cancer cells and may be found in most types of cancer.
  • RAS: About 30 percent of all cancers, including 95 percent of all pancreatic cancers, have known mutations in the RAS family of genes that control cell death and growth.

No targeted therapy drugs have been approved specifically to treat cancers with these mutations. “A number of recognized critical signaling pathways in cancer development, progression and resistance remain very difficult to ‘target’ to influence clinical outcomes,” Dr. Markman says. “The ability to successfully and safely target either or both of these pathways has the potential to be an important advancement in cancer management.”

Many cancers, especially solid tumors, have multiple biomarkers, any one of which may be able to drive a cancer’s growth. Target one biomarker, and another may take over as the driving mutation. And not all the same biomarkers are found in every cancer cell. “As cancer cells grow, they start to develop new abnormalities, mistakes made while the cells are multiplying,” Dr. Bonilla says. These new mutations may make the cancer more resistant to treatment.

Also, doctors need to take steps to prevent the patient from being harmed by the process of targeting a specific biomarker. For instance, patients on a checkpoint inhibitor that targets cancers high in PD-L1 may develop symptoms of autoimmune diseases, such as colitis. “The goal is to find the specific biomarker that every single cell expresses without compromising the normal cells,” Dr. Bonilla says, “because once you tell the immune system to kill a population of cells, it is going to kill all those cells, whether they are good or bad. But if you are able to find the specific biomarker that is the hallmark of this disease and needs to be eliminated, then it’s much easier to find a therapy.”

The discovery of biomarkers has led to game-changing developments in the cancer treatment. Women who learn they have BRCA mutations are now empowered to make potentially life-saving decisions to prevent breast and ovarian cancer. Men with slow-developing prostate cancer can now actively monitor their disease, in part, because their PSA levels can be measured. And research is ongoing to find new biomarkers to help in the treatment of other cancers and diseases, such as diabetes, Parkinson’s disease and heart disease.

“Biomarkers offer an opportunity to apply genomics to population health and see what diseases or conditions people may be predisposed to,” says Pamela Crilley, DO, Chair of the CTCA Department of Medical Oncology. “Am I going to get diabetes? Am I going to get elevated cholesterol? Is there anything I can do about it? Look at hereditary breast and ovarian cancers. The science has led to being able to prevent disease in patients with BRCA1 and BRCA2 mutations. Now we may be able to significantly reduce your risk of disease.”

5 Things Never to Tell Someone Fighting Cancer

This blog was originally published by I Had Cancer on August 6, 2019, here.

Since being diagnosed with non-Hodgkin’s lymphoma in November, I’ve received so much love and support from those around me. Weirdly and surprisingly, I have become closer to some of my friends who were suddenly and unequivocally there for me. I have made new friends from acquaintances who decided it was their job to support me. I have learned to ask for help, which is huge given that I come from the Do Everything Yourself school of thought.

As a prominent member of this school, I also can’t handle unsolicited advice. While most people have been nothing but kind and understanding, some have made it their business to tell me how things “really are”. They think that the fog of cancer is sometimes so all-enveloping that you apparently become confused if not downright mistaken about the why, how and what of your condition. So thank you, casual acquaintances and random strangers in waiting rooms, for enlightening me with your non-specific one-size-fits-all statements. If you’re worried you might be doing this, here are the five hands-down worst things to say to a cancer fighter:

“Sugar feeds cancer”

You will be surprised how, when they find out about you having cancer, some people immediately think “Why”.” And then, almost by magic, their single-track train of thought alights upon “Oh, SUGAR”. The silent killer. The symbol of all that is wrong with society today. Some will whisper, “So, have you changed your diet in any way?” and you know exactly where this is going. Others will just say it outright, like a mantra, “Sugar feeds cancer, y’know.” Initially I was keen to be like, “Yes! Yes! I’m eating so healthily!” Then I thought to myself, I’m the one with cancer here. I’m the one walking around with a 4 inch lump in my chest, sitting in hospital beds while IV fluids pulse their way into me, taking all the pills, feeling all the nausea. I thought, wait a minute. You must be kidding me with your sugar theory.

Because, people, here is the bare-naked truth. It’s a myth. No medical doctor and no reputable cancer institute will tell you that sugar causes cancer, or “feeds” your cancer. One of my oncologists actually had candy on her desk, which frankly might be a little overkill because candy probably isn’t good for anyone. But maybe she was trying to prove a point: You have cancer, have a lollipop! You’ll be fine. FINE. It will not feed it. It will not make it worse, nor will it make it better. Your teeth may rot though.

In the interest of factual accuracy, there has been one recent study using yeast cells (which are similar to cancer cells, but obviously not actual cancer cells) that seemed to suggest that sugar contributed to more growth in these cells. This study has not been replicated so far. And yet, Dr Google will tell you that yes, sugar feeds cancer. The real link here though is that a high sugar diet could make you obese, which is a risk factor for some cancers. THAT’S IT. That is the only proven link at this time.

But let’s assume that it is true, that sugar may actually cause cancer, and then proceed to help it grow. Well, even if this were so, here is my theory: life is short, have it if it makes you happy. Just maybe don’t overdo it, like with everything else. If you ate kale all day it would be just as problematic. But no one is going around saying “You know, kale feeds cancer”. Also, if I want to down packets of sugar from dawn until dusk that is nobody’s business but my own.

“Be positive!”

I don’t know about you, but my first reaction to anyone telling me to “be” anything is, Why the hell should I? You be it! So obviously this one doesn’t go down well with me. And yet, everyone says it.

“You have to stay positive.” There are two things I resent about this statement. Firstly, it implies that by being positive I somehow will have a hand in curing the cancer. Following this thought through, it also implies that if you’re not positive, well, you only have yourself to blame if it all goes hurtling rapidly down the shit-hole. Sound medical thinking there, thanks Denise. Secondly, it implies my outlook on life is unsuitable and that I need to do it this way, the right way. (As a side note, has telling someone to feel a certain thing ever worked? You feel what you feel, no amount of telling is going to change your complex emotions. Just a tip people: Saying it doesn’t make it real. So shut the hell up).

Going back to the outlook on life issue, I feel like I’m generally a cup-half-full girl. I try to believe people are doing their best (except when they tell you sugar feeds cancer), and I strive to find humor and silver linings in the big and little bumps along the way. But I also get down at times. Since being diagnosed, I’ve had moments when I felt like I couldn’t carry on, when I believed I was actually dying, when I had no fight left. When everything seemed bleak, and yes, negative. And even now that I’m cancer-free, I know there is a (small, but real) chance it will come back. That’s not negativity, it’s statistics. Here’s the thing: Be Positive negates the richness and complexity of our human experience, and reduces a heart-breaking, painful, awakening experience to a happy face emoji. I think the reason people say it is that cancer makes them uncomfortable, and they want you to just frozen-smile your way through it so they will feel untarnished. Well, that’s their problem, not mine.

“You will be fine”

Ok. Really?? Will I really be fine?? Because you say so?? A few years ago, I did a doula training course. It was amazing and bonding and revealing and I remember one thing that was emphasized was never to tell a pregnant or birthing woman she will be fine, BECAUSE YOU DON’T KNOW THIS. All you can do is be there to support her, encourage her, and be her advocate. But you can’t tell her how it’s going to pan out. Nobody can, really. So just don’t say this. Just don’t. The other thing is, like Be Positive, it negates the hugeness of the situation. It reduces a life-changing event to “Oh, don’t worry, it will be just fine.” No need to stress. Oh right, thanks for that, I guess I’ll stop crying into my pillow and frantically scribbling my dying wishes, BECAUSE YOU SAID SO.

“Everything happens for a reason”

Oh, and would you care to enlighten me on what this reason you talk of might be? And would it happen to also be the reason why sea turtles swallow plastic bags, mothers and babies die in childbirth, wars happen, and the world is warming up? And if so, pray tell me, should we sit back and watch because we’re all part of a grand plan? If I do nothing, will my cancer just go away if it is meant to? If I die, will that have been part of the plan? If I get better, will there be a reason for that? You weren’t expecting all the questions? I feel like you are getting the point, so I will stop here. And so should you, a couple beats ahead of ever being tempted to say that phrase to anyone going through something as random and pointless as a cancer diagnosis at 36 years of age.

“You should be thankful you have children already”

Not only do you not get to tell me what I should and should not be thankful for, but you don’t get to assume that because I am still alive that from now onwards I should just shut up and be grateful I was spared, and never ever want or desire anything else. I think this statement is perfect in a way because it encapsulates all that cancer steals from you, and all that it brings to life. A cancer diagnosis means that suddenly you go from planning the rest of your life, to trying to figure out if and how you’re going to be alive in a few months’ time. You go from believing you’re only just getting started, to thinking, This is the literal end. So of course when you find that, after all the treatment, you’re still around, you can’t quite believe your luck. You promise you’ll embrace life and all that it has given you with way more gratitude and grace; you say to yourself that your two healthy children, loving husband, friends and family are enough. That the fact you can get out of bed and breathe without coughing, and pick up your child without pain, and walk and swim and (yes!) do cartwheels is the biggest gift and you will forever be thankful. And I am.

But here’s another thing I have learned: feeling desperately sad, or complaining, or having tough days, does not make you ungrateful. More than one thing can co-exist within me. I can be endlessly thankful for my wonderful children, and yet struggle with the fact I will never have another child. We knew this could happen. Infertility, in all shapes and forms, is the worst form of regret – regret over something that you couldn’t possibly have done. There is no redeeming yourself from it. You’re grieving for what never was. So when a doctor asks me if I have children, and I say yes I have two, and I see relief in their eyes and smile, I think, don’t say it, you know nothing about me.