Genetic sequencing could help match patients with biomarker-driven cancer trials, treatments
November 30, 2011 in CancerAs cancer researchers continue to identify genetic mutations driving different cancer subtypes, they are also creating a catalog of possible targets for new treatments.
The University of Michigan Comprehensive Cancer Center and Michigan Center for Translational Pathology (MCTP) recently completed a pilot study aimed at solving the practical challenges involved in quickly and systematically sequencing genetic material from patients with advanced or treatment-resistant cancer in order to match them with existing clinical trials based on the biomarkers identified.
"We're talking about more than just examining a few genes where mutations are known to occur, or even about a hundred genes," says co-lead investigator Dan Robinson, Ph.D., a post-doctoral fellow at MCTP. "We're talking about the ability to sequence more than 20,000 genes and look not just for individual genetic mutations, but at combinations of mutations."
The exploratory study, known as the Michigan Oncology Sequencing Project (MI-ONCOSEQ), found that identifying a patient's "mutational landscape" provides a promising approach for identifying which trials may best help a patient, the researchers say. Their findings were published today in Science Translational Medicine.
"High-throughput sequencing harnesses the latest technological advances to process millions of pieces of genetic information, allowing us to map a cancer's genetic aberrations," says co-lead investigator Sameek Roychowdhury, M.D., Ph.D., a clinical lecturer in hematology and oncology at the U-M Medical School. "Using this technique to identify biomarker-driven treatment options really opens the door for personalized oncology, but it also presents a number of logistical challenges, chief among them making the results available cost-effectively and in a clinically relevant timeframe."
"A decade or two ago, this type of sequencing would have cost many millions or even billions of dollars, but the technology is advancing so rapidly, we're now talking in terms of thousands which makes widespread use a real possibility," he adds.
Cancer can arise from a variety of genetic alterations including rearrangements, additions, deletions and substitutions within the genetic code.
"Different sequencing processes are required to find different types of alterations," Roychowdhury says. "But to be cost-effective, there must be a balancing act between a broad analysis and a deep analysis."
The study began by testing the researchers' sequencing strategy on prostate cancer tumors that had been grown in mice. Later, two patients were enrolled in a clinical pilot: one with colorectal cancer and one with melanoma. Potential clinical trials were identified for both patients.
However, the researchers caution, not all patients will match an existing study. Some patients with a given mutation may be excluded because they have, for example, prostate cancer, but a trial is only enrolling breast cancer patients. The researchers believe that this approach also provides an opportunity to approach clinical trials in a new way, moving from a tissue-specific focus toward genetic aberrations shared across cancer types.
Still, enrolling in a trial does not guarantee a patient will benefit from the treatment, the researchers caution.
Hurdles to widespread implementation include the need for a multidisciplinary Sequencing Tumor Board to interpret the complex sequencing results, management of the necessary computational resources, and a process for dealing with incidental genetic findings revealed by the sequencing such as a risk for hemochromatosis, a genetic disorder that causes the body to absorb too much iron.
Achieving a four-week turnaround time for results is important because that's how long patients are usually required to wait for unsuccessful treatments to leave their systems before starting a clinical trial.
"Once some of the practical and technological hurdles are cleared, we envision an array of mutation and pathway-based trials for available targeted therapies, with eligibility based on molecular assessment," says senior investigator Arul Chinnaiyan, M.D., Ph.D., director of MCTP, Howard Hughes Medical Institute Investigator, and S.P. Hicks Professor of Pathology at the U-M Medical School. "Moreover, if patients are treated with matching targeted therapies and develop secondary resistance, it could also help reveal the mechanisms of resistance and inform future trials for combination therapies."
Chinnaiyan says the work was made possible only by collaboration and teamwork. U-M physicians Moshe Talpaz, M.D., Stephen Gruber, M.D., Ph.D., and Kenneth Pienta, M.D. played key roles in the clinical implementation of this exploratory protocol, he notes.
Researchers hope this type of sequencing will become more widely available over the next 5 to 10 years. Cancer patients are encouraged to speak to their doctors about clinical trial opportunities.
More information: "Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study," Science Translational Medicine, Nov. 30.
Journal reference:
Science Translational Medicine
Provided by
University of Michigan Health System
-
Researchers find genetic rearrangements driving 5 to 7 percent of breast cancers
Nov 20, 2011 |
not rated yet |
0
-
Future of personalized cancer care is promising and near
Apr 19, 2011 |
not rated yet |
0
-
Researchers discover new genes that fuse in cancer
Jan 11, 2009 |
not rated yet |
0
-
New class of cancer drugs could work in colon cancers with genetic mutation, study finds
Apr 25, 2011 |
not rated yet |
0
-
Whole genome sequencing used to help inform cancer therapy
Feb 16, 2011 |
not rated yet |
0
-
Of mice and mental models: Neuroscientific implications of risk-optimized behavior in the mouse
May 25, 2012 |
not rated yet |
0
-
Limits to growth: Scientists identify key metastasis-enabling enzyme
May 22, 2012 |
5 / 5 (4) |
0
-
Seeing is as seeing does: Spatially-structured retinal input in early development of cortical maps
Apr 26, 2012 |
5 / 5 (4) |
1
-
Dreamless nights: Brain activity during nonrapid eye movement sleep
Apr 09, 2012 |
4.4 / 5 (12) |
0
-
Take your time: Neurobiology sheds light on the superiority of spaced vs. massed learning
Mar 28, 2012 |
4.5 / 5 (21) |
3
-
Potential Breakthrough in Seizure Control
11 hours ago
-
Popping/Cracked sternum.
16 hours ago
-
Which Mental Illness Encompasses This Problem?
16 hours ago
-
A question about drug tolerance
May 23, 2012
-
Poor nutrition leading to overeating?
May 23, 2012
-
Math and dyslexia?
May 21, 2012
- More from Physics Forums - Medical Sciences
More news stories
Skp2 activates cancer-promoting, glucose-processing Akt
HER2 and its epidermal growth factor receptor cousins mobilize a specialized protein to activate a major player in cancer development and sugar metabolism, scientists report in the May 25 issue of Cell.
Cancer
May 25, 2012 |
not rated yet |
0
|
Pancreatectomy OK without downstaging from therapy
(HealthDay) -- Pancreatectomy improves median survival in pancreatic cancer patients even when presurgical neoadjuvant therapy does not lead to radiographic downstaging of tumors, according to a study published ...
Cancer
May 25, 2012 |
not rated yet |
0
Common therapies for basal cell carcinoma offer similar survival
(HealthDay) -- For patients with superficial basal cell carcinoma (sBCC), treatment with imiquimod or photodynamic therapy (PDT) results in similar long-term tumor-free survival, according to a review published ...
Cancer
May 25, 2012 |
not rated yet |
0
Cancer may require simpler genetic mutations than previously thought
Chromosomal deletions in DNA often involve just one of two gene copies inherited from either parent. But scientists haven't known how a deletion in one gene from one parent, called a "hemizygous" deletion, can contribute ...
Cancer
May 25, 2012 |
not rated yet |
0
|
New prostate cancer screening guidelines face a tough sell, study suggests
(Medical Xpress) -- Recent recommendations from the U.S. Preventive Services Task Force (USPSTF) advising elimination of routine prostate-specific antigen (PSA) screening for prostate cancer in healthy men are likely to encounter ...
Cancer
May 25, 2012 |
not rated yet |
1
Travel to high altitudes tied to Crohn's, colitis flare-ups
(HealthDay) -- People with inflammatory bowel disease, which includes Crohn's disease and colitis, may be at increased risk for flare-ups when they fly or travel to high altitudes for skiing or mountain climbing, ...
Family history of Alzheimer's affects functional connectivity
(HealthDay) -- Cognitively normal individuals with a family history of late-onset Alzheimer's disease (AD) may display lower resting state functional connectivity in the default mode network (DMN) of the brain, ...
Transvaginal mesh op restores pelvic organ prolapse at price
(HealthDay) -- Transvaginal mesh (TVM) procedures are effective for anatomical restoration of pelvic organ prolapse (POP), but patients report a worsening of sexual function following surgery, according to ...
Tongue analysis software uses ancient Chinese medicine to warn of disease
For 5,000 years, the Chinese have used a system of medicine based on the flow and balance of positive and negative energies in the body. In this system, the appearance of the tongue is one of the measures used to classify ...
Of mice and mental models: Neuroscientific implications of risk-optimized behavior in the mouse
(Medical Xpress) -- Regardless of an organism’s biological complexity, every encephalized animal continuously makes under-informed behavioral choices that can have serious consequences. Despite its ubiquity, ...
Weight struggles? Blame new neurons in your hypothalamus
New nerve cells formed in a select part of the brain could hold considerable sway over how much you eat and consequently weigh, new animal research by Johns Hopkins scientists suggests in a study published in the May issue ...