Sharks Get Cancer, Mole Rats Don't: How Animals Could Hold the Key to Unlocking Cancer Immunity in Humans

Sharks Get Cancer, Mole Rats Don't: How Animals Could Hold the Key to Unlocking Cancer Immunity in Humans

by James S. Welsh, MD

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Overview

This fresh and fascinating exploration of new directions in cancer research focuses on the important role of the immune system in combatting this dread disease. Integrating clues from the animal kingdom, the veterinary clinic, extraordinary human cases, and even embryology, the author-a cancer physician, biologist, and physicist-creates a novel and compelling account of tumor immunology and the promises of immunotherapy.

As the author explains, animals offer us many tantalizing clues about the nature of cancer in humans. Tasmanian devils are on the verge of extinction due to a virulent form of contagious cancer; soft-shelled clams on the East coast of North America are vanishing due to another epidemic of contagious cancer; dogs also contract a contagious cancer but they spontaneously overcome it; and a type of mouse and the homely mole rat are not susceptible to the disease at all.

In humans, there are rare instances of spontaneous cures of advanced cancers induced by radiation. An uncommon form of dwarfism called Laron syndrome confers total cancer immunity on the people who inherit the condition. And recent research suggests that cancer has stolen the secret that shields the embryo against hostile attacks from the mother's immune system.

The author makes a convincing case that what all of these diverse examples have in common is the immune system and its ability or inability to respond to malignancies. He concludes with a review of the exciting research on the human immune system and the development of new treatments that are inducing the immune system to combat and conquer even the deadliest cancers.

Product Details

ISBN-13: 9781633881549
Publisher: Prometheus Books
Publication date: 03/29/2016
Pages: 384
Product dimensions: 5.90(w) x 8.70(h) x 1.10(d)

About the Author

James S. Welsh, MD, FACRO is professor, director of clinical and translational research, and medical director of radiation oncology at the Stritch School of Medicine, Loyola University - Chicago and chief of radiation oncology at the Edwards Hines Jr VA Hospital. He also practices and conducts research in proton beam therapy at the Northwestern Medicine Chicago Proton Therapy Center. He has led research in boron neutron capture therapy and fast neutron therapy at Fermilab when he was the neutron therapy physician at the NIU Institute for Neutron Therapy at Fermilab.

Dr. Welsh has authored over 100 scientific articles and is a sought-after lecturer. Board certified in radiation oncology and neuro oncology, he has worked in the Oncology Department at The Johns Hopkins Hospital, the Human Oncology and Medical Physics Departments at the University of Wisconsin, and was full professor of neurosurgery and radiology at LSU-Shreveport.

He is the current president of the American College of Radiation Oncology and is on the board of directors for the Society for Brain Mapping and Therapeutics. He recently concluded eight years of service on the Advisory Committee for the Medical Uses of Isotopes, which advises the United States Nuclear Regulatory Commission on medical issues.

Read an Excerpt

Sharks Get Cancer, Mole Rats Don't

How Animals Could Hold the Key to Unlocking Cancer Immunity in Humans


By James S. Welsh

Prometheus Books

Copyright © 2016 James S. Welsh, MD
All rights reserved.
ISBN: 978-1-63388-155-6



CHAPTER 1

WHAT JUST HAPPENED?


Allow me to present a very distressing case ...

Daniel — a seemingly healthy, soft-spoken fellow in his early thirties — was about to get news no one ever wants to hear. For years, this athletic, young engineer was eager to soak up some sun and enjoy weekend basketball with his friends. No one can ever know if these habits contributed to the development of an ominous black blotch that began growing on the back of his neck. Like a shark's fin, just beneath the surface was a potential killer.

One day after a pickup game, a friend asked him about a little "freckle" that in some way looked different and angrier. "Hey, Dan, what's that on your neck?" pointing to the dark, discolored patch of skin that slightly resembled tree bark. After seeing it himself with the aid of a couple of mirrors, Daniel decided to have it checked out.

The news was certainly not what he wanted; he had a highly aggressive skin cancer called malignant melanoma. The wide local excision surgical procedure appeared to remove all of the cancer, but melanoma has a notorious tendency to spread far and wide. Most unfortunately for Daniel, within a year his cancer did just that. Despite state-of-the-art combination chemotherapy (meaning multiple drugs given at the same time), the cancer progressed unabated. Almost taunting the chemotherapy, the malignancy soon inundated his body, spreading first to his lymph nodes and then to his lungs. The next line of defense was interferon, an early edition of cancer immunotherapy. Clinical studies had suggested that this then relatively new form of cancer immunotherapy could be of benefit to some melanoma patients. Daniel was not one of them. Interferon can be rough on patients, and the harrowing flu-like symptoms of headache, fever, and malaise were just too intense. He capitulated, electing to discontinue treatment. In defiance of the brief interferon treatment, his disease spread, or metastasized, unrelentingly, as melanoma is wont to do.

Although advanced cancers can ultimately spread practically anywhere, most have preferred sites of initial migration. For example, prostate cancer normally first metastasizes to bone, whereas colon cancer often first spreads to the liver. Melanoma tends to initially involve the lymph nodes, lungs, and liver — and also the brain. At that time, brain metastases heralded an imminent death sentence. Fortunately for Daniel, his MRI (magnetic resonance imaging) studies never showed brain metastases. But melanoma also has a nasty penchant for attacking bone. And in due course, Daniel's inexorable cancer began assailing his skeleton, causing at first only a dull, throbbing ache in his femur (thighbone). Sadly, this pain magnified unremittingly over time to the point where it was all he could think about.

By the time I first saw Daniel in the radiation oncology clinic he was pale, emaciated, weak, and in a wheelchair, unable to walk because of his now lancinating leg pain. He had that all-too-familiar lifeless look: sallow, wasted, and withered beyond his years. Given his recently discovered liver metastases, his medical oncologist had already answered — quite realistically — that dreaded question that no physician wants to address; Daniel had perhaps four more months to live.

Daniel was given heavy doses of morphine, yet the pain pierced through the drug's defensive layer. I could sense that he was suffering quietly as we spoke about his symptoms. We both hoped that I could target a dose of radiation to the bone tumor, thereby shrinking it somewhat and afford him at least a modicum of relief. My first concern however was his risk of a possible pathological fracture — Was his femur in imminent danger of fracturing due to the erosion brought on by the bone-eating tumor? If so, he would require prophylactic surgery to avert a disaster that would likely render him bedridden for the rest of his days. Fortunately the x-rays indicated that the bone had not yet disintegrated to that degree. Nevertheless, cancer was rasping away at this bone, and possibly several others, and needed to be dealt with expeditiously. Before initiating radiotherapy I obtained a bone scan (a nuclear medicine study designed to determine if other bones were involved). If one envisions tumors as tiny light bulbs, Daniel's skeleton lit up like a Broadway marquee.

I offered him palliative radiation therapy to relieve his excruciating pain and to reduce the risk of future pathological fracture. By definition, although this palliative treatment might reduce his pain and forestall a fracture, it was unable to significantly prolong his life. As far as any long-term prospects, it looked like all hope was lost. This radiotherapy was not going to change his prognosis; it was strictly symptom relieving.

I know Daniel tried to pay attention during our consultation, but his mind was unfocussed, distracted by the agony in his leg. I wanted to have an honest and open discussion with him about his prognosis and what the radiotherapy could and could not do. He brusquely concluded the conversation, "Doctor, I just want this pain to go away. When can we get started?"

At the time, a typical course of palliative radiation therapy was around ten to fifteen treatments spread out over two to three weeks. Given his dismal forecast and knowing that he didn't have much time left, in order to accelerate things I decided to treat him with a hypofractionated course of radiation therapy. Hypofractionation is simply the use of fewer, but larger, daily doses of radiation. Although hypofractionation is now recognized as a superior way of treating certain cancers, and today we attempt to "biologically optimize" our radiotherapy courses through hypofractionation, back then in Daniel's case I did this solely to speed the treatment course along.

Daniel's course of radiation therapy consisted of twenty Gray directed exclusively to the rapidly growing tumor gnawing away at his femur. (The Gray is the standard unit of radiation dose. One Gray is one joule of ionizing radiation energy deposited in one kilogram of matter.) It was finished in a few days. At a follow-up only a week after completion of treatment, Daniel was pleased to declare that his pain was already markedly reduced. Not entirely gone by any means, but considerably better than just a week earlier.

Needless to say, I was elated about his newfound pain relief, but I also couldn't help but feel a sense of despair. Why was this previously healthy, young man enduring this tragic early ending? I wished there was something more I, or someone, could do. But there was not. So I did all I could — I renewed his pain medications. I encouraged him to call me if he ever developed any new pain that I might similarly dispel. We scheduled a tentative three-month follow-up with a CT scan (computed axial tomography or CAT scan). I say "tentative" since odds were that he would not be around that long; I most likely would never see him again.

It would be a monumental understatement to say I was surprised when he actually showed up three months later. Seeing him was like being in a waking dream. It was Daniel, but it wasn't. He was now completely pain free; in fact, he said he had discontinued all pain medication shortly after his last visit. And ceasing all those narcotic pain pills (oxycodone and morphine) had another agreeable benefit — he was not constipated for the first time in nearly a year. Mystifyingly, but more satisfying still, he looked somehow healthier. He'd gained a good ten pounds, and more than that, there was a puzzling new vital spark about him.

This was all wonderful, but as to his scheduled follow-up CT scan, I subtly tried to dissuade him. Back then it was customary to obtain a follow-up CT scan after any course of chemotherapy or radiation therapy, and I had reflexively ordered it. But in fact, there was nothing to be gained from the scan — the only thing it could bring was bad news. After all, we had exhausted essentially all available options, so why bother? What would we gain? Nevertheless, despite my gentle protests, Daniel desired the CT scan so I personally walked him over to Radiology. It was a genuine pleasure to be strolling beside this man who only a few months back had been wheelchair-bound.

The Radiology Department was right around the corner, so I invited him to return after his imaging study and we could discuss the results if he was interested. This was way back in the days when everything was still on film rather than on a computer screen. Since I had some time, I strolled over to Radiology early to review the scan with the diagnostic team. At first I was tempted to berate the novice radiology resident for an absolutely amateur error — he must have mixed up the name tags. The scan in front of me was that of a person with no evidence of cancer. Upon closer scrutiny, I could see several small radiographic "scars" or tiny traces of where the tumors once were. On detailed inspection of his recently irradiated thigh bone, I could discern some unmistakable effects of his radiotherapy along with increased ossification, or formation of new bone. The young radiologist had made no mistake. This was in fact Daniel's scan.

Just three months earlier, Daniel's body was riddled with cancer. Today he had a "clean" CT scan with no trace of malignancy anywhere. Astonishing!

Returning to my office, I reviewed the scans with Daniel, who naturally was ecstatic about the great news. Being quite bewildered myself, I asked him a series of probing questions. First I asked him if he had had any recent chemotherapy that I wasn't aware of. The answer was no. What about other early variants of cancer immunotherapy such as interleukin-2 or anything like that? Again, no. I began grasping, "Any special vitamins or over-the-counter supplements?" "Nope." Then I really started stretching. "You didn't go to Mexico and try laetrile or some other esoteric alternative therapy by any chance did you?" The reply was again a resounding NO! He emphatically asserted that aside from a lot of people praying for him, the only thing he did since the radiation therapy was steadily taper off his oxycodone and morphine pain medications.

By now it had become abundantly clear to him that I, his cancer doctor, was at a complete loss as to how to explain this. And although I thought I made it unambiguous at the time of our consultation, it only now truly dawned on him that the radiation therapy I administered was not supposed to do this. Nevertheless, for whatever reason, it apparently had. Daniel didn't seem to care. He was happy — and so was I. A good bit befuddled, but happy.

So what just happened?

Radiation therapy is a local treatment, meaning that it should not have body-wide, or systemic, effects. Like surgery and other local therapies, radiation therapy normally only affects the specific anatomical region being targeted. This differs from systemic therapies such as chemotherapy, which address the entire body from head to toe. A systemic therapy could, in principle, simultaneously induce remission of lung, liver, lymph node, and bone metastases, as in Daniel's case, but local therapies such as radiation therapy, surgery, cryotherapy (localized freezing), or hyperthermia (localized heating) certainly should not. The radiotherapy should have affected only the single thigh bone addressed. Obviously something far larger and unexpected occurred. I began to ask colleagues and read up on the subject of spontaneous remissions and radiation-therapy-induced body-wide remissions. I came across a then rather obscure phenomenon called the abscopal effect.

In an article many decades ahead of its time, the abscopal phenomenon was first described by Dr. R. H. Mole back in 1953. The term is derived from the Greek root "ab" and Latin root "scopus" for "away from the target" and aptly describes what happened. There was an effect — an astounding effect — far from the target. Although it was rather obscure when I first learned of it, if one scans the Internet or does a PubMed search for "abscopal effect" today, one will find scores of hits and recently published papers. In fact, I first described Daniel's case in Discover magazine in 2014, well over a decade after he was treated. Despite the increased awareness and attention, at the time I am writing this, there is still no clear understanding of just how or why this curious and exceedingly rare phenomenon occurs. I, along with most others interested in this phenomenon, are convinced that the abscopal phenomenon represents an extreme example of the immune system's ability to recognize and occasionally overpower even highly advanced cancer.

Daniel came in for routine checkup visits for several more years. Each physical examination and follow-up scan showed no evidence whatsoever of cancer. He gained back all of his lost weight and even proudly packed on some new muscle. A year after his four days of treatment, he was back on the basketball court (albeit with a lot more sunscreen) and again enjoying life. After several years of routine follow-up appointments, Daniel shook my hand firmly and said goodbye, electing not to come back for any more scans or doctor visits. After all, who wants to waste time in the doctor's office when there is so much to be done, so much life to live? For all intents and purposes, he was cured. When I first met him he wasn't expected to live beyond four months — yet here he was, thanking me and striding away four years later.

To date, cases like Daniel's remain extremely uncommon, and there is no obvious rhyme or reason linking them together. Moreover, Daniel's case was extraordinary on another level. Beyond just the rarity of an abscopal phenomenon, his complete response was long lasting. This is a welcomed, but far from guaranteed, outcome with abscopal effects and spontaneous remissions. In fact, the majority are not enduring.

I have only witnessed what appeared to have been durable abscopal effects twice in my clinical career. The other long-lasting response involved a sixty-year-old gentleman with metastatic esophageal cancer. He was diagnosed with adenocarcinoma of the lower esophagus after presenting with progressively worsening epigastric pain (upper abdominal pain just at the lower end of his breastbone, or sternum) and dysphagia (difficulty swallowing). Esophageal cancer is generally considered one of the worst, even when it is caught early. When diagnosed at a more advanced stage (which is all too often), esophageal cancer is considered incurable. His initial medical evaluation included a CT scan, which showed that the cancer had already metastasized to his liver. Because of this diagnosis of stage IV esophageal cancer, curative surgery and definitive radiation therapy were considered futile, and he began chemotherapy alone. (Cancers are typically assigned stages of I to IV, with stage I being the earliest and stage IV being the most advanced.)


(Continues...)

Excerpted from Sharks Get Cancer, Mole Rats Don't by James S. Welsh. Copyright © 2016 James S. Welsh, MD. Excerpted by permission of Prometheus Books.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.

Table of Contents

Contents

Preface, 7,
Chapter 1: What Just Happened?, 9,
Chapter 2: Action at a Distance, 17,
Chapter 3: Disappearing Devils, 23,
Chapter 4: The Devil Himself: Some Diabolical Biology, 25,
Chapter 5: Devil of a Disease, 31,
Chapter 6: The Perfect Parasite, 35,
Chapter 7: A Malignant Malady in Man's Best Friend, 45,
Chapter 8: The Curious Case of Coley's Toxins (Or Sometimes the Treatment Worked), 55,
Chapter 9: The Dog Knows, 63,
Chapter 10: Males Need Not Apply, 69,
Chapter 11: Could Brown Fat Be the Secret to Weight Loss?, 75,
Chapter 12: Gamma Rays and Dinosaur Cancer, 85,
Chapter 13: Cancer of the Clam!, 97,
Chapter 14: Sharks Do Get Cancer (Or How Shark Cartilage Can Kill You), 107,
Chapter 15: Who Truly Doesn't Get Cancer? — Meet the Mole Rats, 115,
Chapter 16: Par for the Course, 121,
Chapter 17: Mighty Mouse to the Rescue!, 125,
Chapter 18: Frodo of Flores, 133,
Chapter 19: A Cancer-Free Clan?, 143,
Chapter 20: Cancer: A Disease of Immune Failure?, 153,
Chapter 21: Malignant Cargo, 165,
Chapter 22: The Power of the Immune System, 171,
Chapter 23: Man Dies of Ovarian Cancer, 179,
Chapter 24: Man's Life Saved by Mosquito Bite, 185,
Chapter 25: Moles, Moles, and More Moles, 197,
Chapter 26: Tumors through the Wormhole, 203,
Chapter 27: The Imposter, 207,
Chapter 28: Competition: The Cause of the Cellular Disease, 221,
Chapter 29: A Standard Model of Molecular Oncology, 227,
Chapter 30: Runaway Train!, 233,
Chapter 31: Order Out of Chaos, 249,
Chapter 32: Immune Theory of Cancer, 255,
Chapter 33: What Can Cows Teach Us about Conquering Cancer?, 265,
Chapter 34: Tough Mothers and Juvenile Delinquents, 273,
Chapter 35: As Crazy as the Quantum Café, 275,
Chapter 36: Connected Dots: Looking Back and Glimpsing the Future, 283,
Acknowledgments, 293,
Appendix: Images with Extended Captions, 295,
Notes, 303,
Glossary, 333,
Bibliography, 351,
Index, 375,

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