Mukherjee's article on oncological treatment is worth a read!

This chart shows how certain genetic mutations found 

in cancers in one part of the body are linked to cancers

found in other body parts. Glad that's all cleared up ... 

Siddartha Mukherjee seems to be everywhere these days, first with his book, "The Emperor of Diseases," about cancer; then with his latest offering, "The Gene: An Intimate History," and now in the pages of the New York Times with a fascinating article about what he calls "improvisational oncology."

Mukherjee's article is worth a read for anybody with ET or another MPN because it delves into the very complicated link between genetic mutation and cancer, and underscores what we and our doctors have known for years: Not all forms of ET respond to the same treatment.

In the "olden days," before the genetic factors of cancer began to be understood, Mukherjee explains that cancers were classified by the parts of the body in which they occurred--lymph, breast, prostate, colon, blood, etc.--and chemotherapies were developed to address cancers in those areas as if they would all respond the same way. If they didn't, Mukherjee writes:

I could draw curtain upon curtain of blame around a patient. When she did not respond to chemotherapy, it was her fault: She failed. Now if I cannot find a tool in the growing kit of drugs to target a cancer’s vulnerabilities, the vector feels reversed: It is the doctor who has failed.

Remember that ET and other MPNs were not even classified as cancers by the World Health Organization until about 2006, and the proliferation of platelets was treated with hydroxyurea (Hydrea), a chemotherapy that was tried on leukemia patients and was found to lower platelet counts. The thinking has been: Lower the platelets, and you lower the risk for clotting, which is the primary health risk for most ET patients. However, hydroxyurea and other chemos have not been successful in curing ET; that's why they call it a "chronic" cancer because there is no cure.

Hydroxyurea is still the go-to drug for ET, but ruxolitinib (Jakafi) is close to being approved for use in JAK2-positive ET patients because it addresses the known "culprit" gene. And that's a good first step, but Mukherjee notes that the picture may be more complicated than we think. Identifying a CALR or JAK2 genetic mutation may only be the tip of a very complicated picture:

Say two identical-looking breast cancers arise at the same moment in identical twins; are the mutations themselves in the two cancers identical? It’s unlikely: By sequencing the mutations in one twin’s breast cancer, we might find, say, 74 mutated genes (of the roughly 22,000 total genes in humans). In her sister’s, we might find 42 mutations, and if we looked at a third, unrelated woman with breast cancer, we might find 18. Among the three cases, there might be a mere five genes that overlap. The rest are mutations particular to each woman’s cancer.

Genetics are only part of the puzzle. Mukherjee explains that some patients with certain types of cancers respond better to treatment if they were first exposed to another type of therapy. And he doesn't even touch on whether exposure to certain chemicals that might play a role in genetic mutation to begin with has bearing on treatment.

Even when doctors think they might have an individualized treatment identified that will work, trying to get insurance companies to pay for off-label uses for drugs can be daunting if not impossible. Researchers are looking for breakthroughs in the data collected from cancer patients that would make "improvisational onconology" more common and effective, but sorting it all out will take some years.

What can you do? Talk to your hematologist about whether your genetic information can be used to help advance research for patients with ET. We are a rare bunch, and the more info that can be collected, the better and quicker we'll all be helped.

Be well!

Related: Your medical records could help others with ET

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