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How Precision Medicine Is Changing Cancer Treatment

Oncologists are able to determine optimal drugs for individual cancers


There’s never been a better time in the history of modern medicine to get cancer treatment, thanks to a bevy of novel therapies grouped under the name “precision medicine” or “personalized medicine.” These methods exploit the unique genetic fingerprint of each individual cancer to create a more precise and effective treatment.

The cornerstone of precision medicine is “targeted therapy,” which means using drugs that target specific molecules inside a cancer cell, particularly those that control cell growth.

The Road to Better Cancer Treatment

To understand how far these targeted therapies have brought us, it’s important to know how we’ve been diagnosing and treating cancer for the last several decades. Here’s a basic explanation:

A suspected cancer — a lump in the breast, a nodule in the prostate or abnormal white blood cells on a lab test — needs to be confirmed with further testing. Typically, this means removing a piece of the abnormal tissue (a biopsy) and sending it to a pathologist, who examines it under a microscope to see if it looks cancerous.

With a modern pathology report of a specific cancer, we don’t just have a mug shot, we have the killer’s DNA.

Once a specimen is determined to be cancerous, the pathologist tries to determine which organ the cancer started in. That information is important because lung cancer that spreads to the brain still looks and behaves like lung cancer, not brain cancer. Breast cancer that ends up in the bones still behaves like breast cancer, not bone cancer.

With the diagnosis of cancer and the “organ of origin” confirmed, the next step is to “stage” the cancer — that is, to figure out how advanced it is.

For example, colon cancer in its earliest stage is just a clump of cells on the end of a polyp. But if the cancer has grown down the stalk of the polyp and into the wall of the colon or spread even further into the lymph nodes of the colon or made it all the way into the liver, then the cancer is in increasingly advanced stages.

Generally speaking, the more advanced a cancer is, the more difficult it is to cure. And nearly every cancer that has spread beyond the organ of origin to another organ (called metastatic or metastasized) is nearly impossible to cure; Hodgkin’s lymphoma and testicular cancer are the exceptions.

This staging process typically includes computerized tomography (CT) scans or positron emission tomography (PET) scans to look for enlarged lymph nodes or evidence of distant spread.

Unfortunately, these scans cannot see on the microscopic level. And because cancer is a microscopic disease, many patients who are thought to have localized cancer at the time of diagnosis, actually have metastatic disease. Precision medicine is addressing this problem.

Macroscopic Approach to a Microscopic Disease

With the diagnosis and staging done, treatment can begin. Commonly, some combination of surgery, chemotherapy or radiation is used to treat all of the cancer identified during staging.

Some patients are cured with this approach, but unfortunately, and far too often, the tumor recurs months or years later — even in cases where we thought “we got it all.”

More chemotherapy can knock the cancer back, sometimes to the point of invisibility, but it doesn’t always kill all of the cancer cells, and months or years later it can come back again. Then, this next “recurrence” is treated with another round of chemotherapy. Sometimes, the cancer returns, quicker than the last time and even more resistant to chemotherapy.

This is where we’ve been: an admittedly imprecise, macroscopic approach to a microscopic disease, using treatment that, despite increasing refinements, remains harsh and often punishing to the body of the patient.

Chemotherapy is a form of carpet bombing, a poisoning meant to kill more cancer cells than healthy cells. But the collateral damage — the side effects of chemotherapy — can be quite a price to pay.

Enter Cancer Genomics

Cancer genomics is the science of analyzing the genetic makeup of a cancerous cell to better understand its true malignant potential. Cancer genomics have altered the field of oncology in substantial ways.

Spurred on by the Cancer Genome Atlas project, which has sequenced the DNA of 11,000 tumors from 33 of the most prevalent cancers, we now have a much more sophisticated way of staging a cancer.

A modern pathology report includes an ever-increasing litany of proteins and genetic markers that tell us far more than a CT scan or simple biopsy about what this particular tumor is capable of doing. We don’t just have a mug shot, we have the killer’s DNA.

In his Pulitzer-prize winning book The Emperor of All Maladies: A Biography of Cancer, oncologist Dr. Siddhartha Mukherjee lays out the rationale for precision medicine/targeted therapy: “A hundred instances of Hodgkin’s disease, even though pathologically classified as the same entity, were a hundred variants around a common theme… Cancers possessed temperaments, personalities — behaviors. And biological heterogeneity demanded therapeutic heterogeneity; the same treatment could not be applied to all.”

Though a stronger pair of binoculars might give you a better look at the bear that is charging you, if all you have is the same old slingshot, the outcome of the encounter won’t change — except that you have more time to anticipate your demise.

A Revolution in Cancer Treatment

But cancer genomics are leading a revolution in cancer therapy, and in particular, in targeted therapies.

The most basic explanation for the complex process of cancer is that a genetic mutation either flips a cell’s “start growth” switch permanently into the “on” position; or it flips the “stop growth” switch into the “off” position. Both scenarios lead to unlimited growth.

The “carpet bombing” chemotherapy of old is rapidly being replaced by new “sniper” drug targeted therapies that enter the cancer cell and restore normal cellular growth. Since these drugs single out cells with genetic mutations, healthy cells are generally unaffected.

The first and perhaps most famous of these targeted therapies is a drug called imatinib (its trade name is Gleevec). Its primary use is in the treatment of chronic myelogenous leukemia (CML), a cancer of the white blood cells. Imatinib works by turning off the BCR-ABL gene, which is the mutated gene that causes most cases of CML.

For many patients with CML, imatinib can transform what was an almost uniformly fatal disease into a chronic illness. Recent trial data show that more than 80% of patients with CML treated with imatinib will survive more than 10 years. Just like with diabetes or hypertension, if you take your medication, you can keep it in check.

The discovery and success of imatinib has ushered in an explosion of second- and third-generation targeted therapies aimed at other cancerous gene mutations. It remains unclear if all of these targeted therapies will ever be able to offer a true cure. But either way, this is the news that so many have been anxiously awaiting.

It has been 47 years since President Nixon signed the National Cancer Act of 1971, commonly referred to as the opening salvo of the “War on Cancer.” Finally, it seems like the tide may be turning.

By Dr. Craig Bowron
Dr. Craig Bowron is a physician and writer in St. Paul, Minn., whose articles have appeared in Slate, the Washington Post, Huffington Post, Minnesota Monthly and other publications. Find him at CraigBowronMD.com.@billcarlosbills

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