Case CCC News - July 29, 2016

July 29, 2016

MESSAGE FROM THE ASSOCIATE DIRECTOR

Brian Bolwell, MD

Chairman, Taussig Cancer Institute, Cleveland Clinic

Associate Director for the Taussig Cancer Institute, Case Comprehensive Cancer Center

bolwelb@ccf.org

Cancer Moonshot Breakfast Panel

Thomas Donohue, President and CEO, US Chamber of Commerce, hosted a Cancer Moonshot Breakfast Panel in downtown Cleveland last Wednesday.

I participated in the panel, along with Toby Cosgrove, MD, President and CEO of Cleveland Clinic, Louis DeGennaro, PhD, CEO of the Leukemia and Lymphoma Society, and Freda Lewis-Hall, MD, Chief Medical Officer of Pfizer.


	Moderator: Jeffrey H. Birnbaum, President of BGR Public Relations; Panelists: Louis DeGennaro, PhD, CEO of the Leukemia and Lymphoma Society; Freda Lewis-Hall, MD, Chief Medical Officer of Pfizer; Toby Cosgrove, MD, President and CEO of Cleveland Clinic; Brian Bolwell, MD, Chairman, Cleveland Clinic Taussig Cancer Institute

A spirited conversation covered a variety of topics, including opportunities in Cleveland from the Moonshot initiative, opportunities in prevention and screening (with special mention of the Case CCC MAPs smoking cessation initiative, and of Vice President Biden's visit to the Langston Hughes facility two weeks ago), the value of research today, given our current knowledge about immunology and genomics, the cost of care, and many other issues.

Members of the national chamber and several business leaders attended, and it was an excellent showcase for our efforts.

MESSAGE FROM THE DIRECTOR

Stan Gerson, MD

Director, Case Comprehensive Cancer Center

Director, UH Seidman Cancer Center

slg5@case.edu

NCCN Publication: Value Access Cost of Cancer Care Delivery

Many of us are concerned with improving the cost of care in the setting of major cancer care centers, such as those at Cleveland Clinic and Seidman Cancer Center and their network sites.

A publication from members of the National Comprehensive Cancer Network (NCCN) on the "Value Access Cost of Cancer Care Delivery" (Nardi EA, et al. J Natl Compr Canc Netw. 2016 Jul), came about after a cancer center leadership retreat and a summit held a year ago in Washington, DC.

This paper presents many salient points about the improved outcomes at NCCN centers and the value patients experience by having comprehensive care in a care path environment.

I contributed the concept of the complexity of interests and the dynamic tension between carte delivery, and the needs and interests of comprehensive cancer centers, patients and their institutions (see Figure 1).

Please have a look.

I hope this clarifies your approach to providing and documenting value in cancer care and in defining and justifying the costs of training, clinical trials, tissue collections to improve care and conduct research, and linking discovery to patent benefit and clinical investigation.

I hope this kicks-off an interesting and ongoing discussion at every level of research, patient care, government oversight, and even the Cancer Moonshot initiative.

MEMBER/RESEARCH HIGHLIGHTS

Mice Survive Brain Cancer Tumors Lacking Key Surface Proteins

A new scientific study has characterized a checkpoint protein that allows certain brain tumor cells to avoid the immune system. Tumors regularly avoid detection by decorating themselves with proteins that mimic those found on healthy cells. This protective shield allows them to grow undetected, often with deadly results. Brain tumors contribute to approximately 17,000 deaths annually with over 4,600 children newly diagnosed each year, according to the American Brain Tumor Association.

Tumors regulate their defensive shields by coordinating cascades of protein signals. These signals are often under the control of central coordinator proteins called serine/threonine kinases.

In the study published in the July 2016 edition of Science (Dorand RD. Science. 2016 Jul 22), researchers studied a protein called cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase that is essential for nerve and tumor cell development. The researchers specifically explored the role of Cdk5 in the development of medulloblastoma, a common, fast-growing pediatric brain tumor.


	Agne Petrosuite


	Alex Huang

The researchers investigated Cdk5 because it is "commonly expressed in abundance and high Cdk5 levels correlate with a worse clinical prognosis in patients with melanoma, brain, breast, and lung cancers," explained Alex Huang, MD, PhD, Case Comprehensive Cancer Center, associate professor of pediatrics, pathology, and biomedical engineering at the School of Medicine, and co-senior author of the study. Agnes Petrosiute, MD, Case Comprehensive Cancer Center, assistant professor of pediatrics at the School of Medicine, was the other senior author. Both are also pediatric oncologists at the Angie Fowler Adolescent & Young Adult Cancer Institute at University Hospitals Rainbow Babies & Children's Hospital, Case Comprehensive Cancer Center.

Researchers discover gene variant associated with esophageal cancer

Researchers at University Hospitals Case Medical Center have discovered that a rare genetic mutation is associated with susceptibility to familial Barrett esophagus (FBE) and esophageal cancer, according to a new study published in the July issue of JAMA Oncology ( Fecteau RE. JAMA Oncology, 2016).


	Amitabh Chak

Amitabh Chak, MD, Case Comprehensive Cancer Center, University Hospitals Case Medical Center's Seidman Cancer Center and Case Western Reserve University School of Medicine, and colleagues set out to identify novel disease susceptibility variants in FBE in affected individuals from a large multigenerational family.


	Kishore Guda

The team, led by Dr. Chak along with collaborating senior author Kishore Guda, DVM, PhD, also of the Case Comprehensive Cancer Center, used targeted next generation gene sequencing to find a rare mutation (S631G) in FBE in the uncharacterized gene VSIG10L that segregated with disease in affected family members. Functional studies revealed that this mutation disrupts maturation of the normal esophageal lining. more>

Case Western Reserve University Researchers Block Common Type of Colon Cancer Tumor in Mice

In a study published online in Nature Communications (Hao Y, et al. Nat Commun. 2016 Jun 20), researchers from the Case Comprehensive Cancer Center and Case Western Reserve University School of Medicine identified why colorectal cancer cells depend on the non-essential amino acid glutamine. This understanding led them to discover the possibility of tumor suppression by "starving" tumor cells. The team's findings lay groundwork for human clinical trial planned for August 2016.


	Zhenghe John Wang

Led by Zhenghe John Wang, PhD, co-leader of the GI Cancer Genetics Program at the Case Comprehensive Cancer Center and professor of genetics and genome sciences at Case Western Reserve University School of Medicine, researchers studied a subset of colorectal cancer cells containing a genetic mutation called IK3CA. They were interested in determining whether or not the common PIK3CA mutation contributes to changes in cancer cell metabolism, such as how nutrients like glutamine are processed. The researchers found that colorectal cells with the PIK3CA mutation broke down significantly more glutamine than cells without the mutation. The researchers identified several enzymes involved in the process that are more active in the mutant cancer cells than in other cell types, explaining the increased need for glutamine. These enzymes become overactive in the mutant cancer cells due to a cascade of signals led by the protein encoded by mutant PIK3CA gene. This finding represents a novel and important link between the common PIK3CA mutation and altered glutamine metabolism in cancer cells.

When the researchers lowered the amount of glutamine available to mutant cancer cells growing in laboratory dishes, the cancer cells died. This discovery led the team to investigate the effects of blocking glutamine availability in mice with colorectal cancer tumors containing the common PIK3CA mutation. Wang and colleagues found that exposing these mice to a compound that blocks glutamine metabolism consistently suppressed tumor growth. They did not observe the same effect on tumors without the mutation. Together, these results provide a promising new therapeutic avenue to suppress growth of colorectal tumors with the PIK3CA mutation. The researchers have filed a patent application based on the unique mechanism of tumor suppression they have identified and the work is available for licensing.


	Neal Meropol

"This study provides the basis for a colon cancer treatment clinical trial that will be started in the summer at the University Hospitals Seidman Cancer Center," according to Neal Meropol, MD, Associate Director for Clinical Research at the Case Comprehensive Cancer Center, Dr. Lester E. Coleman, Jr. Professor of Cancer Research and Therapeutics, chief of the division of hematology and oncology, and principal investigator for the trial. The phase I/II study will test the effects of a glutamine metabolism inhibitor in patients with advanced colorectal tumors. more>

ASH honors medical students, residents

The American Society of Hematology (ASH) announced the names of 15 medical students and 15 residents selected to receive the 2016 ASH HONORS (Hematology Opportunities for the Next Generation of Research Scientists) Award. The awardees included two trainees being mentored by Case Comprehensive Cancer Center members:

Parisa Khalighi

Medical student, Case Western Reserve University School of Medicine

"The role of PAR4 polymorphisms in sickle cell disease"

Mentors: Marvin Nieman and Jane Little

Rushad Patell, MD Resident, Cleveland Clinic

"Identifying predictors for stroke in patients with cancer and atrial fibrillation; a cohort study"

Mentor: Alok A Khorana

The ASH HONORS Award aims to support the career development of talented North American medical students and residents interested in hematology. Recipients receive a stipend of $5,000 to conduct either short-term (up to three months) or long-term hematology research projects (between three and 12 months) and $1,000 each year for two years to support their attendance at a program orientation at the ASH annual meeting. Each HONORS participant will have an ASH member research mentor who will assist and oversee the awardee's work and progress.

MARK YOUR CALENDARS

Great Lakes Breast Cancer (GLBC) Symposium

Registration is open for the 2nd Great Lakes Breast Cancer (GLBC) Symposium, Thursday, September 8 through Saturday, September 10, 2016. The event will be held at the Herberman Conference Center at UPMC Cancer Pavilion in Shadyside, Pittsburgh, PA.

The GLBC Symposium is made possible through collaboration between the University of Pittsburgh Cancer Institute (UPCI), the Case Comprehensive Cancer Center (Case CCC), and The Ohio State University (OSU) Comprehensive Cancer Center (James Cancer Hospital and Solove Research Institute).

The 2016 GLBC Symposium aims to increase collaboration between these three cancer centers in the area of breast cancer research and clinical trials. A keynote talk will be given by Dr. Joyce Slingerland (University of Miami Health System).

We very much look forward to your attendance and participation in this meeting, and we especially encourage you to bring students and fellows.

We encourage you to book your room as soon as possible, as it is football season and we expect the hotels to sell out fast. Accommodations are available at the Hyatt House Pittsburgh/Shadyside, located one block away from the symposium venue site. Book your room before August 7 by visiting the hotel's website or calling the hotel directly at 1.888.545.8207 and reference the GLBC symposium.

Cancer Stem Cell Conference 2016

Sep 20-23 Hilton Cleveland Downtown

In 2014, the National Center for Regenerative Medicine created the international Cancer Stem Cell (CSC) Conference to foster new collaborations across national and international boundaries.

This conference will address the translation of bench-top science to patient care. CSC 2016 is guaranteed to offer cutting-edge presentations in a variety of specialized areas within the field. Join us for this 4-day summit and network with scientists and clinicians advancing cancer stem cell research and therapeutic applications.

CSC 2016 will feature:

Renowed speakers from over 25 different institutions
Preconference Workshop (Trainee Career Development)
Meet the Editors (Cell Stem Cell and Nature Cell Biology)
Young Investigator Awards (Junior level faculty and below)
Over 100+ posters
15 Short Talks (selected from abstracts submissions)

VeloSano Bike to Cure

Best of luck to all the riders participating in the VeloSano events this weekend. Be safe and have fun!

We Need Volunteers for our Cheer Station!

Team Case Comprehensive Cancer Center will support a Cheer Station on Euclid Avenue near Kelvin Smith Library. Our team will cheer on VeloSano Riders by ringing cowbells, holding signs, and making noise to keep everyone motivated as they approach the last leg of their ride. We need as many people as possible, so please encourage your friends, families and kids to join in the fun. Plus, participation qualifies you to apply for pilot funding! Email Tracy Rehl (tracy.rehl@case.edu) to sign up.

Cheer Station Shifts

July 30: 11 am - 1 pm

July 30: 12:30 - 2:30 pm

July 30: 1 - 3 pm

Team Sponsors

Thank you to our team sponsors: Spangenberg, Shibley, & Liber; Taft, Stettinius, & Hollister; Blanda Orthopedics; Majic Family Fund; Peter Osenar; TOLI (The Tavern of Little Italy); New Belgium Brewing Co.; Ziegler Metzger, LLP; top supporters: Jerry & Helen McDonough and Peter Osenar; Cheer Station sponsor: Paradise Flower Market.

IN THE NEWS

Cleveland matters for Vice President Biden's Cancer Moonshot: Stanton L. Gerson (Opinion)

cleveland.com - Jul 27, 2016

Opinion piece written by Dr. Stanton L. Gerson, director of the Case Comprehensive Cancer Center and University Hospitals Seidman Cancer Center, and professor at Case Western Reserve University's School of Medicine.

Vice President Joe Biden's Cancer Moonshot has galvanized the country in a nonpartisan way as few recent events have. And it should. Virtually every family is, has been, or will be affected by cancer. We all have a stake in seeing the project succeed.

Cleveland matters for the Moonshot. We have outstanding health care centers and research programs, among the best anywhere. The vice president visited us several weeks ago to highlight our role in cancer prevention. We were honored by the recognition and accept the challenge to build on what we have accomplished to date...

First Cancer Patient in Ohio Receives Proton Therapy Treatment

Yahoo Finance - Jul 26, 2016

Mevion Medical Systems, the leader in compact proton therapy, is announcing that University Hospitals (UH) in Cleveland used the industry-leading MEVION S250 proton therapy system to treat its first patient, a 24-year-old woman with rhabdomyosarcoma, a rare form of sarcoma. The proton therapy treatment made history by being the first in the state of Ohio.

The new proton therapy center is located on the main campus of UH, directly between UH Rainbow Babies & Children's Hospital and UH Seidman Cancer Center, part of the elite National Cancer Institute-designated Case Comprehensive Cancer Center at Case Western Reserve University.

"At UH, we aim to provide the most advanced cancer treatment options, and the addition of our MEVION S250 furthers our commitment to bringing the best cancer care possible to our patients" said Nathan Levitan, MD, president of UH Seidman Cancer Center. "We are particularly excited by the fact that this will be one of the few proton therapy centers in the world to be physically connected to a children's hospital, so both children and adults will be able to benefit from the unmatched precision of proton therapy."

Not a Death Sentence

The Jerusalem Post - Jul 25, 2016

The Third Friends of Israel Urology Symposium held earlier this month at the Tel Aviv Hilton was attended by some 450 urologists, oncologists, uro-oncologists, uro-patholothists and uro-radiologists to discuss recent developments in the field. One of the leading prostate cancer experts to attend was Prof. Eric Klein, a urologist, surgeon and oncologist who heads the Glickman Urological and Kidney Institute at the Cleveland Clinic in Ohio. A guest of Oncotest Teva (which makes technology used to predict how the disease will proceed according to the patient's genetic profile), Klein said in an interview with The Jerusalem Post that he has visited Israel several times to participate in medical conferences and has ties with Israeli researchers and physicians, some of whom trained at the Cleveland Clinic.

Pennell Provides Perspective on EGFR-Targeted Agents in NSCLC

OncLive - Jul 21, 2016

As more patients with non-small cell lung cancer (NSCLC) are being tested for EGFR mutations and more therapies are being approved by the FDA, a new challenge is rising in the field, explains Nathan Pennell, MD, PhD. "The question is, 'What is the best one to use?'" says Pennell, who gave a lecture on EGFR-positive NSCLC during the 2016 OncLive State of the Science Summit on Metastatic Non-Small Cell Lung Cancer. "We actually have 3 approved first-line EGFR TKIs in the United States. We have erlotinib (Tarceva), gefitinib (Iressa), and afatinib (Gilotrif), which is a second-generation irreversible pan-HER inhibitor."

Study sees rise in advanced prostate cancer cases

CBS News - Jul 19, 2016

The number of new cases of advanced prostate cancer in the United States has soared by about 72 percent in the last decade, according to a new study, but not all experts agree with its findings. The report, published in in Prostate Cancer and Prostatic Diseases, a journal from Nature, prompted researchers to question whether a recent trend of fewer men being screened may be contributing to the rise... Dr. Eric Klein, chairman of the Glickman Urological & Kidney Institute at Cleveland Clinic, said he believes the USPTF's recommendation against PSA screening played a big role in the increase in metastatic prostate cancer cases seen in the study. He, too, finds the task force's prostate screening advice problematic, citing the development of more accurate blood and urine tests and the general movement away from a rush to treat early stage prostate cancers, with more doctors opting instead for the wait-and-see approach of active surveillance.

Conflict of Conscience

ASH Clinical News - Jul 19, 2016

Editor's Corner commentary by Mikkael Sekeres, MD, MS, Director of the Leukemia Program at the Cleveland Clinic in Cleveland, Ohio, and editor-in-chief of ASH Clinical News.

FUNDING OPPORTUNITIES

Limited Submission: Gabrielle's Angel Foundation

The Case Comprehensive Cancer Center has been invited to submit applications for the Gabrielle's Angel Foundation 2016 funding program.

The Foundation accepts only one application per category/per institution:

One Mainstream/Conventional research project
One Integrative Medicine research project

Eligibility Criteria

Have an MD or PhD
Hold a junior faculty position at a 501(c)(3) teaching research institution
Hold the designation of Assistant Professor (Associate Professors may not apply)
Have institutional support in form of tenure track OR be an independent junior faculty member
Have held their current position no longer than five years
Clearly state that they have both independent research projects and independent resources
Have preliminary results and/or publications from their independent laboratory

Nomination Process

To be considered for the nomination, submit a one-page LOI and biosketch to Gillian Irwin (gmi@case.edu) by Thursday, August 4, 2016.

View RFA (pdf)

DoD Breast Cancer Research Program Breakthrough Award Levels 3 and 4 II

Pre-Application Deadline: Sep 14

Invited Application Deadline: Dec 8, 2016

Applications to the Fiscal Year 2016 Breast Cancer Research Program (BCRP) are being solicited for the Defense Health Agency, Research, Development, and Acquisition Directorate, by the U.S. Army Medical Research Acquisition Activity.

The intent of the Breakthrough Award is to support promising research that has high potential to lead to or make breakthroughs in breast cancer. The critical components of this award mechanism are: Impact: Research supported by the Breakthrough Award will have the potential for a major impact and accelerate progress toward ending breast cancer. The impact may be near-term or long-term, but must be significant and move beyond an incremental advancement. Applications must articulate the pathway to making a clinical impact for individuals with, or at risk for, breast cancer, even if clinical impact is not an immediate outcome. Research Scope: Research proposed under this award mechanism may be small- to large-scale projects, at different stages of idea and research development.

Damon Runyon Physician-Scientist Training Award

Deadline: Dec 1, 2016

Applications are currently being accepted for the Damon Runyon Physician-Scientist Training Award. Physician-scientists who are both clinically trained and expert researchers are essential to the successful translation of scientific discovery into more effective patient therapies. They have the unique capacity to blend their insights from treating patients and working in the laboratory in a way that enables and accelerates medical advances. However, the pipeline of physician-scientists is dwindling. The decline in this vital cadre of cancer researchers is occurring at a time when cancer research holds the greatest promise of improving survival and quality of life among cancer patients. A growing shortage of physician-scientists means that major laboratory research discoveries will progress to patient application ever more slowly. If the shortage continues unabated, some may not reach patient application at all, thus presenting a crisis in cancer research.

Eligibility

Physician-scientist applicants (MDs only) must have completed their residencies and clinical training, be U.S. Specialty Board eligible prior to the award start date, and be able to devote at least 80% of their time and effort to Damon Runyon-supported research. MD/PhDs are not eligible to apply.

The candidate may not have had more than three years of postdoctoral laboratory research experience.

Candidates must apply with a Mentor. The Mentor's role is to foster the development of the applicant's knowledge, technical and analytical skills, and capacity for scientific inquiry in the field of basic or translational research chosen by the candidate and in which the Mentor is an outstanding figure. The Mentor will also serve as an advocate for the applicant at departmental, institutional, and other relevant professional levels.

Only one fellowship application will be accepted from a Mentor per review session; there is no limit, however, to the number of applications from an institution.
No more than two awardees will be funded to work with the same Mentor at any given time.
Eligible candidates may apply up to two times.

Letter of Commitment from Institution/Department

A letter endorsed by both the Dean or Center Director, and the Head/Chair of the Department, should (1) confirm the applicant's and Mentor's academic appointments, (2) state the institution's commitment to support the applicant's research efforts, the nature of the support that will be provided, and guarantee a minimum of 80% protected time for the applicant's research to fulfill the terms of the award. The Foundation will monitor the awardee's protected time during the course of the award to ensure that this commitment is being met. Please let us know if you are planning to apply for this award so we can help prepare a letter of support.