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Graeber - BREAKTHROUGH: immunotherapy and the race to cure cancer

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    BREAKTHROUGH: immunotherapy and the race to cure cancer
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From theNew York Timesbestselling author ofThe Good Nursecomes an empowering and accessible story of the discoveries of the tricks cancer uses to avoid the immune system, and the important new therapies already unleashing the immune system to fight -- and beat -- the disease.
Four years in the writing,The Breakthroughis an exciting read about the discoveries which received the 2018 Nobel Prize winning discoveries in October, and a dramatic and exciting turning point in our relationship with a disease that has for too long defined us.

For decades, scientists have puzzled over one of medicines most confounding mysteries: Why doesnt our immune system recognize and fight cancer the way it does other diseases, like the common cold?
As it turns out, the answer to that question can be traced to a series of tricks that cancer has developed to turn off normal immune responses-tricks that scientists have only recently discovered and learned to defeat. The result is what many are calling cancers penicillin moment, a revolutionary discovery in our understanding of cancer and how to beat it.
In THE BREAKTHROUGH, Graeber guides readers through the revolutionary scientific research bringing immunotherapy out of the realm of the miraculous and into the forefront of twenty-first-century medical science. As advances in the fields of cancer research and the human immune system continue to fuel a therapeutic arms race among biotech and pharmaceutical research centers around the world, the next step-harnessing the wealth of new information to create modern and more effective patient therapies-is unfolding at an unprecedented pace, rapidly redefining our relationship with this all-too-human disease.
Groundbreaking, riveting, and expertly told, THE BREAKTHROUGH is the story of the game-changing scientific discoveries that unleash our natural ability to recognize and defeat cancer, as told through the experiences of the patients, physicians, and cancer immunotherapy researchers who are on the front lines. This is the incredible true story of the race to find a cure, a dispatch from the life-changing world of modern oncological science, and a brave new chapter in medical history

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Some names and other identifying details have been changed to protect the privacy of the individuals involved.

Copyright 2018 by Charles Graeber

Cover design by Christopher Lin. Cover image copyright by Getty Images.

Cover copyright 2018 by Hachette Book Group, Inc.

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First Edition: November 2018

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Library of Congress Cataloging-in-Publication Data has been applied for.

ISBNs: 978-1-4555-6850-5 (hardcover), 978-1-4555-6849-9 (ebook)

E3-20181203-JV-PC-COR

The Good Nurse: A True Story of Medicine, Madness, and Murder

For Diann Waterbury Graeber

My mother and our survivor

It seemed to me then, and still does, that some such built-in immunologic mechanism ought to exist for natural defense against cancer in humans.

L EWIS T HOMAS , 1982

Cancer is alive. Its a normal cell, mutated and changed, and it continues to change in the body.

Unfortunately, a cancer drug does not mutate or change.

A drug may poison or starve the cancer for a time, but whatever cancer cells remain will continue to mutate. It only takes one. The drug dances with cancer, but cancer dances away.

As a result, these types of drugs are unlikely to ever truly cure cancer.

But we have killers in our bodies, and scouts and soldiers, a dynamic network of cells more nimble than any cancer. This is our immune system, a living defense as old as life itself.

This system mutates. It adapts. It learns and remembers and matches an innovating disease step for step.

Its our best tool to cure cancer.

And we have finally discovered how to unleash it.

This is the breakthrough.

The good physician treats the disease; the great physician treats the patient who has the disease.

S IR W ILLIAM O SLER , 18491919

U ntil very recently weve had three main methods for treating cancer. Weve had surgery for at least three thousand years. We added radiation therapy in 1896. Then in 1946, chemical warfare research led to the use of a mustard gas derivative to kill cancer cells. Those poisons were the foundation for chemotherapy.

These cut, burn, and poison techniques are currently estimated to be able to cure cancer in about half of the people who develop the disease. And thats remarkable, a true medical accomplishment. But that leaves the other half of cancer patients. Last year, in the United States alone, that translated to nearly six hundred thousand people who died of the disease.

The fight was never fair. Weve been pitting simple drugs against creative mutating versions of our own cells, trying to kill the bad ones while sparing the good ones and making ourselves sick in the process. And weve been doing that for a very long time.

But now we have added a new and very different approachone that doesnt act directly on cancer, but on the immune system.

Picture 2

Our immune system has evolved over 500 million years into a personalized and effective natural defense against disease. It is a complex biology with a seemingly simple mission: to find and destroy anything thats not supposed to be in our bodies. Cells of the immune system are on constant patrol, hundreds of millions of them circulating throughout the body, slipping in and out of organs, searching out and destroying invaders that make us sick and body cells that have become infected, mutated, or defectivecells like cancer.

Which raises the question: Why doesnt the immune system fight cancer already?

The answer is, it does, or tries to. But cancer uses tricks to hide from the immune system, shut down our defenses, and avoid the fight. We dont stand a chance, unless we change the rules.

Cancer immunotherapy is the approach that works to defeat the tricks, unmask cancer, unleash the immune system, and restart the battle. It differs fundamentally from the other approaches we have to cancer, because it does not act upon cancer at all, not directly. Instead it unlocks the killer cells in our own natural immune system and allows them to do the job they were made for.

Picture 3

Cancer is us. Its the mistake that works. Cells in the body regularly go rogue, their chromosomes knocked out by particles of sunlight or toxins, mutated by viruses or genetics, age, or sheer randomness. Most of these mutations are fatal to the cell, but a few survive and divide.

99.9999 percent of the time, the immune system successfully recognizes these mutant cells and kills them. The problem is that rogue 0.0001 percent cell, the one that the immune system doesnt

Picture 4

Cancer is different. It does not announce itself like the flu or any other disease, or even a splinter. It doesnt seem to sound an alarm in the house of the body, or provoke an immune response, or show symptoms of immune battle: no fever or inflammation or swollen lymph glands, not even a sniffle. Instead, the tumor is suddenly discovered, an unwelcome guest that has been growing and spreading out, sometimes for years. Often by then it is too late.

To many cancer researchers, this apparent lack of immune response to cancer meant that the goal of helping an immune response to cancer was futilebecause there was nothing to help. Cancer was assumed to be too much a part of our selves to be noticed as non-self. The very concept of cancer immunotherapy seemed fundamentally flawed.

But throughout history, physicians had recorded rare cases of patients whose cancers apparently cured themselves. In a prescientific age these spontaneous remissions were seen as the work of magic or miracle; in fact, they are the work of an awakened immune system. For more than a hundred years researchers tried and failed to replicate those miracles through medicine, to vaccinate or spark an immune response to cancer similar to those against other formerly devastating diseases like polio, smallpox, or the flu. There were glimmers of hope, but no reliable treatments. By the year 2000, cancer immunologists had cured cancer in mice hundreds of times, but could not consistently translate those results to people. Most scientists believed they never would.

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