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What’s the biology of your cancer?

Pathologist Jeffrey Ross, MD, who has expertise in genomic profiling, consults with other Upstate doctors and leads a monthly meeting in which he reviews and teaches about the ongoing care of individual patients at Upstate. Pathologist Jeffrey Ross, MD, who has expertise in genomic profiling, consults with other Upstate doctors and leads a monthly meeting in which he reviews and teaches about the ongoing care of individual patients at Upstate. He is shown with some laboratory samples. (photo by William Mueller)

Treatment is moving from 'one size fits all' into the modern era of personalization


Among people who receive a cancer diagnosis, up to 8 percent won’t ever find out in which organ their cancer began. Because the cancer has metastasized, or spread, before it is discovered, it usually comes with a poor prognosis.

This type of cancer – known as CUP, or carcinoma of unknown primary – is among the most challenging types of advanced cancer to treat.

Some doctors will prescribe chemotherapy, with the goal of shrinking the tumor or improving symptoms.

A growing number of doctors will say, “We may not be able to know where your cancer started, but what’s the biology of your cancer?”

Up to a third of people diagnosed with CUP will have a genetic marker for which a new medication is available, says Jeffrey Ross, MD, an assistant professor of pathology and urology at Upstate and the medical director for Foundation Medicine in Cambridge, Mass. “But you won’t find it unless you sequence the tumor.”

Each person’s cancer has a unique combination of genetic changes, and tumor DNA sequencing is done to identify those changes. Some genetic alterations or mutations can help guide treatment plans, possibly pointing to medications that can prolong a person’s life by months or years.

This new generation of anti-cancer drugs is being developed together with diagnostic tests, which help predict which patients can be helped by a particular drug. For instance, some targeted therapies are effective for people only if their cancer cells have a specific mutation that causes the cancer cells to grow a certain way. Some immunotherapy medications will work only when there are a certain number and type of genetic alterations.

Ross says Medicare and most health insurers pay for at least one of the sequencing tests in use today. However, not all of the potential therapies are covered.

Tumor DNA sequencing is not meant for everyone who has cancer. And, it can’t help everyone with a CUP diagnosis.

Unfortunately, sequencing often reveals targets for which drugs do not yet exist, Ross explains. In the year 2020, about one-quarter to one third of those who undergo tumor DNA sequencing will learn of a potential treatment.

Ross says he expects one day about half of those tested will find new treatment options.

Currently, though, many people undergo batteries of tests, in hopes of identifying the primary tumor from which their cancer has spread. Without answers, they are diagnosed with CUP. Many doctors will recommend anti-cancer treatment or palliative care to relieve these patients’ symptoms. Only about one in 10 of these patients survives a year.

“Standard treatment for CUP has not changed in decades so, if we can change the outcome for the one in three patients with targetable mutations identified by DNA profiling, that could have an important impact on CUP therapy,” says Ross, one of the leaders of the molecular laboratory in the Central New York Biotech Accelerator at Upstate.

“CUP is a bit of a pariah because people don’t understand it and assume that nothing can be done,” he says. “We need to change that attitude and encourage clinicians to look for and treat the drivers of each patient’s disease as shown by DNA profiling.”

Ross reported on his research at the European Society of Medical Oncology last fall in Barcelona, a conference that attracted more than 28,000 attendees. Two other Upstate professors presented work there, including Gennady Bratslavsky, MD, on the genetic landscape of two specific types of cancerous tissue, and Jeffrey Bogart, MD, on radiation treatment plans for patients with small cell lung cancer.

Possible treatment: What's the difference?

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules that are involved in the growth, progression and spread of cancer. They differ from chemotherapy in that:

-- they act as specific molecular targets associated with cancer; most standard chemotherapies act on all rapidly dividing normal and cancerous cells.

-- they are designed to block tumors cell proliferation; many chemotherapies were identified because they kill cells.

-- most are available as pills; some chemotherapy medication are pills, but most are infusions.

Immunotherapy is a type of cancer treatment that helps your immune system fight cancer. It's delivered through an infusion. There are several types, including immune checkpoint inhibitors, t-cell transfer therapy, monoclonal antibodies, treatment vaccines, immune system modulators and others. Different immunotherapies are given intravenously, in pills or capsules, in creams that are rubbed onto the skin, or directly into the bladder.

Remember this:

Get yourself to an academic medical center where tumor DNA sequencing is an option if you have a cancer whose origin cannot be determined.

Up to one-third of people with CUP – the medical abbreviation for carcinoma of unknown primary – have an individual cancer characteristic that can be treated with an immunotherapy and/or targeted cancer therapy, but not until the biology of the tumor is known.

Approvals for new therapies are happening with such speed that keeping track of what’s available, its side effects and interactions requires expertise.

How is tumor DNA sequencing done?

A sample of your tumor and, in some cases, a sample of your healthy cells must be removed either during surgery or through a biopsy.

Your samples will be sent to a specialized lab — such as the one at Upstate Medical University — where researchers will isolate your DNA and then use a machine called a DNA sequencer to “read” it. They will then analyze the sequence of your DNA to determine if there are any genetic alterations that make your tumor susceptible to certain treatments. They may also examine the DNA sequence of your healthy cells to determine if you have any inherited mutations that can influence treatment decisions.

Based on your tumor’s unique genetic alterations, the specialized lab may generate a report that lists treatments to which your tumor is likely to respond.

Source: National Cancer Institute


Here are some places to learn more about the modern era of personalized cancer care:

-- The American Society of Clinical Oncology website at ASCO.org. Click here, or under “research & guidelines,” look for “reports & studies,” and click on “Clinical Cancer Advances 2019.”

-- The American Cancer Society website at cancer.org. Click here, or use the search bar to type in “carcinoma of unknown primary.”

-- The National Cancer Institute website at cancer.gov. Click here, or type carcinoma of unknown primary” in the search field.

-- Jeffrey Ross, MD, did a podcast for Upstate’s “HealthLink on Air.” Click here, or find it at Healthlinkonair.org by searching for “Jeffrey Ross” or “immunotherapy.”

This article is from the spring 2020 issue of Cancer Care magazine.