by Amy Keller
Updated 5 yearss ago
One of the most surprising findings emerging from mathematical models is that blasting cancers with as much chemotherapy as a patient can survive might not always be a good idea. "The classic mechanisms for therapy for 50 years have been to trot out your biggest, baddest drugs, give it in your highest dose possible, as quickly as possible. The idea is you really want to whack it," says Dr. Robert Gatenby.
But there's a problem: Tumors are not giant masses of identical cells. They contain cell variations that actually compete against each other for survival. Toxic chemotherapy wipes out the cells that are susceptible to the drugs. Drug-resistant cancer cells survive by adapting, however. The cells that adapt are usually weaker in some ways than the ones that die, but since the chemo has wiped out their cancer-cell competitors, they have an open field in which to proliferate.
"If you give a lot of drugs and kill off the sensitive guys, the only ones that are left are the ones that are resistant. So while they might not be as fit as the other guys, there's no competition, so they just grow," says Gatenby.
And the cancer recurs in a more aggressive, drug-resistant form.
What the mathematical models suggest is what Gatenby calls "adaptive therapy" -- enough chemo to reduce the tumor, but not too much. Allowing some drug-sensitive cells to survive means they'll suppress the growth of the drug-resistant cells.
Farmers, he says, have used this approach for decades. Dumping massive amounts of pesticides on crops simply accelerates the development of drug-resistant insects, so farmers leave a section of their field untreated. Some drug-sensitive bugs survive, delaying the evolution of a completely resistant bug population.
Gatenby and his team are already experimenting with their less-is-more approach in treating breast and prostate cancers. It's worked in both models and in mice, he says, and they're hoping to start two clinical trials sometime this year to test it out on patients with metastatic cancer. If it works as he expects, Gatenby believes many incurable cancers could end up being managed as a treatable, chronic disease.
The biggest hurdle Gatenby anticipates is that "people and doctors don't like it" because they don't want to give up on the idea for a complete cure. "If there's a possibility for a cure, I'd say go for it. But in tumors where the probability of a cure is basically zero, there's essentially no precedent for curing a patient, I would argue, don't kid yourself!"
Gatenby and his team use mathematical tools like game theory, which predicts gains and losses in competitive scenarios, to try to figure out ways to outwit cancer. The idea, he says, it not to sit and wait and see how a tumor reacts to a particular treatment, but rather to anticipate what it will do.
One example that has worked with some cancers, Gatenby says, is combining immunotherapy and chemotherapy. In some cases, he says, a drug that boosts the patient's immune system doesn't kill all the cancer cells, but the cells that avoid the body's immune response do so by taking on properties that make them more vulnerable to chemotherapy. In the end, the cancer isn't completely eradicated, Gatenby says, but the approach produces a kind of uneasy stalemate that keeps it in check.
Cancer cells in a tumor aren't all the same, and the different variations compete with for survival even as the overall tumor grows.
Traditional, massive doses of chemotherapy wipe out all the cells that are sensitive to the drugs. Others, however, adapt in some way.
While surviving cells may be weaker than those the chemo killed, they now have no competition, and can grow freely.
The cancer recurs, but now in a form that doesn't respond to drugs at all.
In microbiology, students learn that RNA is a "messenger molecule" whose job is to carry protein-making instructions from a cell's nucleus to the cytoplasm, the fluid area between the nucleus and the cell membrane. But only about 3% of RNAs actually perform those functions, and until about a decade ago, many scientists viewed the other 97% of "non-coding" RNAs as cellular "junk" -- extraneous material.
Over the past decade, however, a flurry of research has revealed that some non-coding RNAs perform important functions: They switch genes on and off and play a role in the regulation of a wide scope of processes, from the development of an embryo to the development of cancer and other diseases.
At Sanford-Burnham Medical Research Institute at Lake Nona, researchers led by Dr. Ranjan J. Perera are looking at the role that various non-coding RNAs play in the development of skin cancer melanoma and prostate cancers. Perera and collaborators at the University of Queensland in Australia have honed in on one long, non-coding RNA (lncRNA) called SPRY4-IT1 that is elevated in melanoma cells, where it promotes cellular survival and invasion. They also report that melanoma cells have lower levels of another small non-coding RNA, called miR-211.
Perera and his team hope that by identifying early prognostic markers of melanoma and prostate cancer they will one day be able to diagnosis cancers earlier, through simple blood tests as opposed to painful biopsy procedures, and devise better treatments.
While lung cancer is the leading cause of cancer deaths in the United States, more than two-thirds of all lung lesions occur in the distant regions of the lung, making diagnosis and treatment a challenge.
Conventional screening methods, such as traditional bronchoscopy, can only reach lesions in the main bronchial tubes, and patients must often submit to more invasive and risky surgical procedures to get a diagnosis.
Cleveland Clinic Florida is one of several Florida hospitals using a new GPS-like technology to extend the reach of a conventional bronchoscope to lesions deep in the lungs with minimal trauma to the patient.
The procedure, known as electromagnetic navigation bronchoscopy, begins with a CT scan, which is loaded into planning software that creates a 3-D roadmap of the lungs. Once the bronchoscope is placed through the patient's mouth and into the airways of the lungs, a flexible catheter containing electromagnetic sensors is advanced through the bronchoscope.
Those sensors then guide the physician to the target lesion, where the doctor can collect tissue samples for testing and diagnosis. The procedure, which is performed in an outpatient setting, is also offered at North Florida Regional Medical Center, Brandon Regional Hospital, Mercy Miami Hospital and other Florida institutions.
Last year, more than 16,700 Floridians were diagnosed with prostate cancer. At Cleveland Clinic Florida, prostate gland removal is performed in the hospital's new, state-of-the-art operating room, which combines magnified video projection with a 3-D robotic surgical system. The operating room is the first of its kind in Florida and the second in the nation.
Florida Blue, the state's largest insurer, is experimenting with new cancer-oriented accountable care organizations, launching one last May in conjunction with Baptist Health South Florida and Advanced Medical Specialties. This year, the insurer is teaming up with Moffitt Cancer Center to create an accountable care organization for cancer patients in the Tampa Bay area.
The collaborations aim to improve care while cutting costs by shifting to a "value-based" reimbursement structure. Rather than billing in the typical fee-for-service manner, doctors and hospitals earn financial incentives for providing good quality care while keeping costs down.
Since taking the reins as director of the University of Miami's Sylvester Comprehensive Cancer Center one year ago, Dr. Stephen Nimer has recruited 11 faculty members, formed committees to assess everything from patient experience to the hospital's portfolio of clinical trials, and worked to expand or develop a number of services at Sylvester, including programs for breast, lung and prostate cancers and hematological malignancies.
Behind those moves is Nimer's goal of getting Sylvester designated as a National Center Institute facility -- and the substantial funding that comes with the designation. Currently, Moffitt Cancer Center in Tampa is the only NCI-designated facility in the state.
"We want to have many more outstanding programs than is required to apply for the NCI designation," says Nimer, a leukemia and stem cell transplant researcher and physician lured from Memorial Sloan-Kettering in New York.
"My goal down here is to build the clinical programs and to help build the research programs and bring in new faculty who will leverage the expertise we have on both the science and the clinical side so we meet all the criteria for NCI designation."
Sylvester Cancer Center, which is 40 years old this year, once had NCI designation, but lost it in 1996 after it was unable to keep up its various programs. Today, Sylvester is the only academic cancer center in south Florida and serves between 6 million and 7 million people.
Nimer says the benefits of regaining NCI's stamp of approval include an influx in research dollars and patient access to clinical trials available only at NCI-designated cancer centers. The elite distinction would also help Sylvester recruit more top-tier cancer physicians and researchers.
New technology at the University of Florida Proton Therapy Institute at Shands Jacksonville is offering hope to patients with metastatic cancer, the spread of the disease from one region of the body to another. Using a new machine called Vero doctors at UF are able to track tumors in real time with image-guided technology and deliver high-dose radiation therapy with a high degree of precision. Dr. Paul Okunieff, a professor and chair of the UF department of radiation oncology and director of the UF Shands Cancer Center, says Vero is particularly useful in targeting tumors that may be moving as the patient breathes or with each heartbeat. "This enables us to deliver the optimum dose of radiation to the tumor, destroying it from the inside out while sparing healthy tissues surrounding it," says Okunieff. The treatment, which is usually given during a five- to 10-day period, has been particularly effective in treating patients who are in an early stage of metastatic disease, with five or fewer lesions. Okunieff, while still at the University of Rochester, was the principal investigator of a study that demonstrated promising long-term survival for patients, and breast cancer patients in particular, with limited metastases. Okunieff says the technology is helping UF's Metastatic Cancer Program achieve its goal of changing metastatic cancer from a terminal condition to one that is manageable or even curable.
It took 20 years and an estimated $3 billion for an army of scientists to decode the human genome, the so-called "genetic blueprint" of human life. Today, the once laborious task of unraveling an individual's genetic makeup can be accomplished in just a few weeks, at a cost of a few thousand dollars.
That technological revolution is one of the driving forces behind the rise of personalized medicine, which seeks to tailor a patient's care based on his own individual genetic makeup, says Dr. Alexander Parker, a nationally known kidney cancer epidemiologist at Mayo Clinic in Florida and the associate director of Mayo's new Center for Individualized Medicine.
"We're in an exciting age now. We can do things at the genetic level that are literally mind blowing," says Parker. Instead of looking at single genes, Parker says, "we can look at an entire genome for an entire individual" as well as the entire genome of that cancer to "see what's going on."
At Mayo, Parker says he and his colleagues believe genetic sequencing can help them better answer questions "that cover the entire natural history of cancer" -- everything from why it develops and how it can be better diagnosed to why it's more aggressive in certain patients and why some patients experience side-effects from treatments while others don't.