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Cleveland Clinic Names Two Cancer Advances among Top 10 Medical Innovations for 2016

Eastman, Peggy

doi: 10.1097/01.COT.0000475703.73966.a8
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In its annual list of the top 10 most powerful innovations for the coming year, Cleveland Clinic named two advances in cancer research: genomics-based clinical trials for cancer and other serious diseases, and cancer screening using protein biomarker analysis.

This is the 10th annual listing Cleveland Clinic has released; the announcement closed the medical center's 2015 Medical Innovation Summit, held at the Cleveland Convention Center.

Listed as #2 in importance, genomics-based clinical trials hold the promise of bringing treatment based on precision medicine to cancer patients, especially end-stage patients who may not have much time to wait for drugs targeted to their specific cancer, commented Charis Eng, MD, PhD, Chair of the Cleveland Clinic Genomic Medicine Institute, which houses the Center for Personalized Genetic Healthcare.

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CCF PTEN Study

Eng is the principal investigator of an internal Cleveland Clinic Foundation research study, the CCF PTEN study, designed to accurately assess germline PTEN mutation frequency among incident invasive breast cancer cases; mutations of the PTEN gene play a role in many cancers. The implications of the study findings will be used for medical management of patients and education of their family members.

The findings will also be used to identify the frequencies of mutations in novel genes within the PTEN pathway that are related to breast cancer. Eng is studying diverse mechanisms of PTEN inactivation not only in breast cancer but also in thyroid and endometrial cancers. She has noted that her multidisciplinary laboratory approaches are aimed at identifying novel targets for therapy and prevention.

“An average 10 percent of all cancers are due to strong alterations in genes which predispose individuals to multiple cancers, often at young ages, and that can be inherited and passed on to their children,” Eng said. “Our cancer genetics and genomics research fulfills the adage ‘knowledge is power’ in empowering us to promote our own and our families' health and well-being.”

Nima Sharifi, MD, the Kendrick Family Endowed Chair for Prostate Cancer Research in the Department of Cancer Biology at Cleveland Clinic, discovered that a genetic mutation enables prostate cancer cells to produce their own hormones for fuel, thus rendering them resistant to traditional hormone-deprivation therapies. He has noted that he plans to use funding from an award given to him by the Prostate Cancer Foundation to create a prognostic test to determine which patients have the mutation and are thus at high risk of death from aggressive prostate cancer.

“This kind of strategy of personalized medicine will help us further our understanding of this deadly disease,” he said.

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NCI-MATCH Trial

In other genomics research overall, the National Cancer Institute's pioneering NCI Molecular Analysis for Therapy Choice (NCI-MATCH) trial, now open for enrollment, analyzes patients' cancerous tumors to determine whether they contain genetic abnormalities for which a targeted drug exists (actionable mutations) and assigns treatment based on that abnormality, if present (OT 8/25/15 issue). NCI-MATCH has 10 arms, and aims to obtain tumor biopsy specimens from about 3,000 patients initially.

The drugs to be used are approved by the Food and Drug Administration or are investigational therapies that have shown efficacy against tumors with a specific alteration or alterations. NCI-MATCH can add new treatments or drop treatments over time; the trial plans to test more than 20 drugs. NCI-MATCH uses an advanced DNA sequencing test; an enrollment goal is that 25 percent of patients in the study will have rare cancers.

While usually it takes a long time to ramp up an NCI trial, that is not the case with NCI-MATCH, noted NCI Acting Director Douglas Lowy, MD: “The accrual is far faster than anticipated,” Lowy told attendees recently at the annual meeting of the Association of American Cancer Institutes. “We are planning to add more arms to the trial. ... Interest in the trial has been without precedence.”

President Obama's Precision Medicine Initiative allocated $70 million to NCI for scaling up efforts to identify genomic drivers in cancer and using those findings to develop new therapies.

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Cancer Screening via Protein Biomarkers

The second cancer-related advance, cancer screening via protein biomarkers, was ranked as number 6 in importance on the Cleveland Clinic list. Studying cancer proteomics, the complement of proteins produced by an organism or cellular system, holds the promise in real time of “finding tell-tale proteins that provide insight into the biological processes of cancer development,” according to NCI.

Because proteins drive disease physiology, screening for cancer with a new platform of validated protein biomarkers—anticipated in 2016—could be a boon to early detection. The FDA has stressed that all biomarkers used in the clinic must be rigorously evaluated and validated.

The Lerner Research Institute (LRI) of the Cleveland Clinic maintains the Proteomics Core, a protein-sequencing facility that uses tandem mass spectrometry methods to sequence and identify proteins. Research from LRI has revealed that resilient cancer stem cells in glioblastoma secrete the protein periostin, which helps tumor cells survive and thrive.

In a second study, investigators discovered that the protein Sema3C, which is abundant in glioblastoma, helps cancer cells survive and invade healthy tissue. These protein biomarkers, periostin and Sema3C, could eventually prove useful in cancer screening and early diagnosis.

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Biomarker Panel for Colorectal Cancer

The use of a blood-based protein biomarker panel for the detection of colorectal cancer could be especially helpful, since the majority of cases of colorectal cancer are preventable by early detection and removal of precancerous polyps. Because many people resist stool-based screening and colonoscopy, a reliable, non-invasive blood-based screening test would be welcome in the clinic.

In an Australian study published in PLOS One earlier this year (DOI: 10.1371/journal.pone.0120425), researchers led by Kim Y.C. Fung, PhD, evaluated seven single biomarkers in the serum of colorectal cancer patients and age- and gender-matched controls, and found a significant difference between the controls and the colorectal cancer patients.

The researchers identified a panel of three biomarkers of the seven that discriminated between the controls and the colorectal cancer patients with 73 percent sensitivity at 95 percent specificity when applied to either of the two cohorts:

  • Insulin-like growth factor binding protein 2 (IGFBP2);
  • Dickkopf-3 (DKK3); and
  • Pyruvate kinase M2 (PKM2).

The team concluded that this three-biomarker panel may have the potential to be used as a blood-based diagnostic screening tool for early (Stages I and II) colorectal cancer.

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IOM Report

The road to treatments based on genomics and proteomics has been a promising but bumpy one. As noted in the Institute of Medicine report “Evolution of Translational OMICS: Lessons Learned and the Path Forward”: “Increasingly, drugs are being developed to target specific disease subtypes or mutations, and companion diagnostic tests are being developed to identify the subsets of patients most likely to respond or at least likely to suffer serious side effects.”

But, the report adds, “Despite great promise, progress in translating such ‘omics-based’ tests into direct clinical application has been slower than anticipated. This has been attributed to the time-consuming, expensive, and uncertain development pathway from disease biomarker discovery to clinical test; the underdeveloped and inconsistent standards of evidence to assess biomarker validity; the heterogeneity of patients with a given diagnosis; and the lack of appropriate study designs and analytical methods for these analyses.”

However, the IOM report concludes, patients themselves increasingly recognize the promise of molecularly driven medicine and are looking to science to develop reliable clinical tests that accurately diagnose disease and predict response to treatments.

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Other Top Medical Innovations in the Cleveland Clinic List

The other top medical innovations listed for 2016 are the following:

  • Rapid development of epidemic-battling vaccines;
  • Gene editing using the CRISPR (clustered regularly interspaced short palindromic repeats) technique;
  • A water purification system for prevention of infectious disease;
  • Cell-free fetal DNA testing;
  • Naturally controlled artificial limbs;
  • First treatment for female “hypoactive sexual desire disorder”;
  • Frictionless remote monitoring, such as needle-free glucose monitoring via a biosensor; and
  • Neurovascular stent retrievers—small devices inserted via a catheter that seize and remove clots from stroke patients.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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