Personalized Cancer Medicine: Are We There Yet?
Dr. Richard Frank—
There is alot of talk in the world of cancer today about "personalized cancer medicine" (PCM). PCM means that a cancer patient's treatment is specifically tailored to that individual's cancer based on the results of sophisticated genetic analyses, such as determining the complete DNA sequence (called the genome) of the cancer. PCM aims to deliver what oncologists and patients want and need: the right treatment for the right patient. This of course is the ideal. Some cancer organizations have declared that we are now 'in the era of personalized cancer medicine.' And start-up biotech companies are offering (for a price not covered by insurance) to perform a "genomic analysis" of an individual's cancerous tumor. So, it is timely and important to ask, Are we there yet? Are we at the point of being able to treat each patient uniquely based on the complete DNA structure of their cancer? The answer is actually no, we are not there yet. Still, mainy things can be learned about the cancer treatment of today and tomorrow by discussing PCM.
The Origins of Cancer and The Need for PCM
At its most basic level, cancer represents the conversion of a previously healthy, well-behaved cell in the body into a cell that can grow, spread and survive better than all the other cells. This transformation can only come about when the DNA of the cell becomes irreversibly altered. Not just a little altered but VERY altered. Recent analyses of the complete DNA sequences from a patient with leukemia and another with lung cancer disclosed tens of thousands of differences in the cancer DNA compared to the patients' normal cell DNA. The investigators whittled down these many differences to the dozen or so key genetic changes that drive the cancers and which could be targeted by drugs. But when they tested other patients with the same type of cancer (such as acute myeloid leukemia or AML), they discovered that although some changes are shared, many others are unique to each individual case. Truly personalized cancer medicine then would involve determining the DNA changes in each person's cancer and having at our disposal the medicines capable of blocking the key bad genes that are overactive and restoring the good ones that have been lost (these medicines are yet to be discovered, the main reason why we are not ready for PCM). Many good minds believe that being able to achieve this level of specificity in cancer treatment will lead to cures and billions of research dollars are being invested in this approach. No doubt, PCM will revolutionize cancer treatment. But if we are not at they point of PCM, where are we in the treatment of cancer?
The Modern Era of Cancer Treatment: Targeted Therapies
Today's cancer treatments do tailor therapies to patients to some extent. A traditional example would be the use of hormone therapies such as tamoxifen or letrozole to treat breat cancer that is estrogen receptor positive. A more up to date example would be to test a lung cancer for a mutation in a gene called EGFR and if a mutation is present, treat the patient with erlotinib (Tarceva) rather than chemotherapy; erlotinib specifically blocks the activity of EGFR. These treatments and many others are called "targeted therapies" because they target one or a few specific molecules in the cancer cell. Many cancers today are treated with targeted therapies, often in conjunction with chemotherapy. Additional examples include the use of Herceptin plus chemotherapy to treat breast cancer that is "Her2 positive;" the use of Rituxan to treat B-cell non-Hodgkin's lymphoma; and Imatinib (Gleevec), nilotinib or dasatinib to treat chronic myelogenous leukemia. The newest advances include PARP Inhibitors to treat breast and ovarian cancers and RAF Inhibitors to treat melanoma.
In fact, nealy all of today's advances in cancer treatment are based on the development of targeted therapies. Yet, although targeted therapies represent major advances in how cancer is treated, their main deficiency is that they are not leading to cures. Better outcomes, longer lives, better quality of life for sure, but not the eradication of cancer (so far). The reason is that each drug only targets a few of the genes that drive a cancer. And there are dozens that must be targeted. But it is not so easy as just combining two, three or four targeted therapies; there are often more toxicities with this approach and less success than anticipated.
The Way Forward
We are presently in the era of targeted therapies and this approach will continue for many years. Many new types of targeted therapies will be approved to treat cancer in the years to come. Clinical trials are widely available that are testing these new medicines and I encourage all cancer patients to inquire as to their availability. At the same time, researchers are making strides in reducing the cost and improving the speed of determining all of the DNA changes in an individual cancer. But this analysis will only be useful if we can act on the results: if the medicines are available that block the bad genes and restore the good genes that have been lost and if we know how to combine all these medicines in people without doing more harm than good. This will take many years to work out in clinical trials. For now, pay attention to advances in cancer, participate in clinical trials and don't pay for sophisticated, costly tests that your oncologist does not recommend.
I realize these issues are complicated. I am happy to answer your question, please email me!
Richard C. Frank, M.D., is director of cancer research at the Whittingham Cancer Center of Norwalk Hospital, medical director of Mid-Fairfield Hospice, and Clinical Assistant Attending at Weill Cornell Medical College. He has been appointed cancer expert for WebMD and was named a “Top Doc” in the New York Metro area by Castle and Connelly.
Further Reading:
Hi Dr. Frank,
Do you think PCM is the best way to approach the problem, or are there any different methods of cancer treatment research you would like see investigated?
Meg Brooks
Dear Margaret,
Personalized cancer medicine should relate to many aspects of “the person.” This would include various biologic aspects of their body, such as their immune system, markers of inflammation and the functioning of their vital organ systems. Of course, their psychological profile is extremely important and should never be neglected. Cancer is more than just the cells that are cancerous but also the body’s response to the cells. The future is wide open in terms of tailoring therapies to the individual.
Dr. Frank
Dear Dr. Frank,
Thank you for clarifying the distinction between two popular terms in survivorship: PCM (personalized cancer medicine) and Targeted Therapies.
In your response to Margaret, you highlight a common source of confusion over the adjective “personalized” in the context of survivorship. The “personalized medicine” you discuss in your post refers to the highly sophisticated technology that will allow clinicians to tailor a therapy to the genome of a patient’s cancer cell.
This is in contrast to the “personalized medicine” that physicians and nurses have been offering since the beginning of medicine: namely, treating every patient as a unique individual. Such care is an essential element of compassionate care.
Ironically, at a time when the highly technical PCM you describe is within view, many people are complaining that modern medicine has become impersonal and compassion is being lost.
As a physician/survivor, I agree that no matter how medicine changes in the future, the clinician-patient bond is at the heart of healing. We — clinicians and patients, alike — must do all we can to help preserve compassion in medicine.
I also appreciate the plug for clinical trials. I was a subject in the Phase I and Phase II clinical trials of Rituximab for lymphoma back in the early 1990s.
Even though I am not cured of my cancer, I am living a good life, thanks to Targeted Therapy.
With hope, Wendy
Wendy S. Harpham, MD
Dear Wendy,
Thank you so much for your wonderful reply. The need to treat each patient as an individual, I hope, will never change in the practice of medicine, especially oncology. An oncologist has to weigh not just the genes and biology of the cancer but the age, medical condition, lifestyle and goals of each patient when deciding on a therapy. Although insurers are moving towards algorithm based care, in a one size fits all model, I believe this is inferior medicine and actually makes it very hard to practice good cancer medicine.
For example, I recently saw a 90 year old woman, non-smoker with lung cancer. I wanted to prescribe erlotinib (a pill) but the insurer refused to cover the costs because the patient did not yet receive and progress through chemotherapy treatments. We are still battling this out. I have had to call, write letters and submit the results of clinical trials to try to change their minds and allow the “right” treatment that does not fit their algorithm. Meanwhile, a month has gone by. Things will only be getting worse as far as I can tell.
My very best wishes for your continued healthy survivorship (Your term!).
Rich
I think we’ve come a long way with cancer research, and personalized treatment may finally be the proper action
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Dear Dr. Frank,
Hi?
I am TaeJin Ahn, a bioinformatist in Korea.
I’ve looking at a good application of bioinformatics technology with combination of next generation sequencing.
I’ve reached the same conclusion that we’re at targeted therapeutics era but soon will reach personalized medicine.
I’m so sure for this, but I’m not sure when is it realized.
Do you have any good suggestion for the time of its realization ?
I’ve also found CollabRx, Foundation Medicine, companies aiming at true PM. just FYI.
Thank you.
Dear TaeJin,
Thank you for your message and great work. More than likely, personalized cancer medicine will occur a disease at a time. For example, tailoring lung cancer medicines to mutations in EGFR or ALK (see my post on that)today will likely be expanded to many more targets as they are discovered. A genome wide approach as I wrote about seems much farther in the future.
Regards,
Dr. Frank