Reviewed by: Yeong Sek Yee & Khadijah Shaari
10, Jalan SS 19/1K, 47500 Subang Jaya, Selangor.
Tel: 03-56342775 / 019-3278092
THE AUTHOR:Dr. Richard C. Frank, MD,an oncologist, is the Director of Cancer Research, Whittingham Cancer Center, Norwalk Hospital, Norwalk, CT, and Medical Director, Mid-Fairfield Hospice, Wilton, CT.USA.
WHAT THE BOOK IS ABOUT: As expected, the whole book is devoted mainly to describing the virtues of conventional treatment of the various types of cancers via surgery, radiation, chemotherapy, targeted therapies and hormone therapies. However in the chapter on “How Cancer Grows and Cancer Treatments at Work”,Dr. Frank gives an explanation as to why chemotherapy may not work for you. We summarize the main points below:-
CANCER CAN GROW UNPREDICTABLY (pages 124-126)
a) Although cancer appears to develop in an organized fashion when viewed from the outside, if we were to go inside a tumour with a little magnifying glass and monitor the movement of cells and the integrity of DNA; we would see a much more chaotic situation.
b) As a cancer develops and grows, the DNA that guides it along is prone to change…. as a cancer grows, its genetic makeup becomes diversified, which leads to a diversity of cell types within it…. cancer is not a collection of identical cells.
c) The tendency of a cancer to generate cells with different capabilities explains many of the dreadful aspects of cancer that patients find so hard to grapple with:
- Why it can spread from one location to another,
- Why it stops responding to a treatment that was working,
- Why it can return when it was in remission
The reason is that every cancer, whether it arises in the lung, breast, prostate, bone marrow, or elsewhere, contains different populations of cells that have distinct properties.
d) A cancerous tumour does not contain billions of identical clones. Cancer could never develop in this way because it must avoid the immune system’s attack on it, live in areas of low oxygen tension, and compete with the rest of the body for vital nutrients.
e) Inside any tumour are cells that are living and cells that have died. There are cancer cells capable of reproducing many others, called cancer stem cells, and cells completely devoid of this capacity. Cancer’s diversity is generated early. By the time it is diagnosed, some cells may already be capable of metastasizing and others may be able to withstand a particular cancer treatment. This is the basis of cancer’s resistance to treatment i.e. chemotherapy (see section “Why Do Cancer Treatments Sometimes Fail?”).
f) When new cancer cells are generated inside a tumour, some will be hearty enough to survive and others will not be. If some cells survive the treatment, then it is mainly because their DNA contains the necessary alterations that help them resist the chemotherapy drug; this population of cells will then expand, and the compositions of the cancer will again change. (page 126)
g) …. when a cancer returns after being declared in complete remission, it is because a few cells were different enough to stay alive after a treatment killed nearly all the other cells; this difference could have been present from the start of treatment or it could have developed as a response to it. Whichever occurred, it is cancer’s ability to diversify and adapt its DNA that enables it to survive. (page 126)
WHY DO CANCER TREATMENTS SOMETIMES FAIL? (PAGES 188-190)
(a) Drug resistance or the growth of cancer in the face of ongoing or recently completed treatments represents the main barrier to cure for many cancers…. (page 188). In many instances, oncologists cannot specify why a person’s cancer develops treatment resistance…. treatment resistance is probably the most complicated area of oncology. (page 189).
(b) The root cause of a cancer relapse lies in the fact that cancer is not an accumulation of exactly the same cells but rather a mixture of cells with differing properties. Some may have sensitivity to certain drugs and be killed by them, whereas others are resistant to those drugs. The resistant population will survive treatment and in time be detected as a cancer relapse. (page 189)
(c) Drug resistance may be present in an untreated cancer or emerge in response to therapy…. the innate adaptability of cancer cells and how they can sometimes outwit an effective therapy by altering their DNA or other molecules. This property explains the acquisition of resistance during a cancer’s growth. (pages 189-190)
(d) Chemotherapy may lose its effectiveness when cancer cells activate a protein that pumps the drugs out as soon as they enter the cells; targeted therapies may lose their ability to control their targets when those receptors and signalling proteins mutate and morph into different shapes; hormone therapies may stop controlling cancer growth when estrogen or androgen receptors undergo a shape change or get massively overproduced, overwhelming the drugs meant to neutralize them. (page 190)
(e) Several types of cancer have been found to contain a very small population of cancer stem cells, which are believed to be responsible for continually replenishing the pool of cells in a tumour. It turns out that an additional property of these cancer stem cells is their natural resistance to chemotherapy and other cancer treatment.
(f) Some chemotherapy drugs (as well as radiation therapy) may contribute to (or directly cause) the development of new cancers many years after treatment (page 174). And it has been known for decades that chemotherapy alone cannot eradicate the advanced stages of the most common cancers (page 175).
TARGETED THERAPIES: (PAGES 175-180)
The current hot trend is to offer targeted drugs like Erbitux (for colorectal, head and neck cancers), Rituxan (for lymphoma), Herceptin (for breast cancer), Tarceva(for lung cancer), Sutent (for kidney cancer) and etc. Once in the bloodstream, they act like heat-seeking missiles, locating cancer cells wherever they lurk and gripping onto them via one specific receptor target (among thousands of receptors) that projects from the outer surface of the cells. The result is that the receptors stop transmitting growth signals inside the cells (page 177).
(a) Are targeted therapies “magic bullets”?
According to Dr Frank …..” although targeted therapies were developed with the hope that they would be magic bullets that would neatly eradicate cancer through selective targeting of one critical molecule, in general they have fallen short of this lofty goal. No cancer is considered curable by treatment through a targeted therapy alone… (page 180) The reason for the muted success of targeted therapies is that most cancers are caused not by one genetic derangement but by several; no one target functions as an Achilles heel. “(page 180)
(b) Do targeted therapies cause side effects?
“Like any other drug taken for any purpose, unintended effects may occur with these medications. Generally speaking, targeted therapies are easier to tolerate – less hair-loss, smaller declines in blood counts, less nausea… still, substantial side effects may occur with some targeted therapies, and they tend to increase the toxicities of chemotherapy when used in combination.” (page 182)
Finally, angiogenesis inhibitors (like Avastin, Sutent, Nexavar, Thalomid) constrict blood vessels not only inside tumours but also in other parts of the body. As a result, they often cause some degree of high blood pressure and are associated with an increased risk for kidney damage, bleeding, stroke and coronary artery blockage. (page 183)
In conclusion, we quote two very relevant statements by Dr. Frank:-
i. Efforts to blast away metastatic cancers with mega doses of chemotherapy have fallen short because they do not root it out but rather cause more harm than good: the cancer is still present and the patient is sicker than ever. (page 143)
ii. Even though billions of dollars are invested in cancer research every year, most new drugs in the research pipeline will extend life rather than the silver bullets that pierce the heart of cancer. (page 145)
THE FOLLOWING ARE SOME WORDS OF ADVICE BY DR FRANK ON NUTRITION, pages 102-110.
Although the whole book is about conventional cancer medicine, Dr Frank did make some notable comments/advice on diet and cancer (not the”eat anything you like” type). We summarise the main points as follows:-
a) …the contribution of diet…to the development of cancer is so large that if behaviours could be changed, many cancers could be avoided altogether… (and many oncologists will be without jobs). Almost 30 years and a great deal of research later, the link between poor nutritional habits…and the development of cancer have been solidified…
b) A large and ever-growing number of studies indicate…..cancers are highly influenced by one’s pattern for living: a diet high in red meat and animal fats and low in fruits and vegetables…contributes an unhealthy pattern for living that often leads to major illness.
c) Diet can promote or inhibit the formation of cancer…through:-
(i) The presence of carcinogens in food (which can be natural constituents or man-made additives);
(ii) The generation of carcinogens by cooking…when foods are smoked, fried, or grilled, polycyclic hydrocarbons are produced;
(iii) The increased exposure of the body to carcinogens by a diet low in fiber, which slows down bowel movement;
(iv) ”over-nutrition” or excess body weight.
d) Excess body fat promotes the development of cancer because it leads to two important changes in the body’s chemistry. page 109)
(i) The development of the insulin resistance syndrome or metabolic syndrome; and
(ii) The increased production of estrogen.
e) More fat, more estrogen, more breast cancer. The ovaries are the main source of estrogen production in menstruating women. When ovarian function ceases upon menopause, estrogen is still produced in the female body, although in lesser amounts. In post-menopausal women, fat becomes the main estrogen factory, with higher body weights correlating with higher estrogen levels…and estrogen stimulates the growth of the breast and uterus. Just as the normal cells in these tissues multiply in response to estrogen, so do (most) cancers derived from them.(page 109)
f) The connection between fat and breast cancer is in part caused by the fact that fat contains an enzyme called aromatase that increases estrogen production. So even after menopause, when the ovaries have ceased producing estrogen, the hormone still gets made in the body. That’s why a class of medicines called aromatase inhibitors (AIs)…. blocks aromatase from working and thereby drastically reduces the levels of estrogen in the bloodstream. Examples of AIs are femara (Letrozole), anastrazole (Arimidex) (page 110)
Note: This book was published in april 2009. ISBN no: 978-0-300-1510-2