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May 2013

Genomics of ACC: New Findings


A team of researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City has published a very significant article in the journal Nature Genetics entitled "The mutational landscape of adenoid cystic carcinoma". Led by Dr. Timothy Chan, the team performed DNA sequencing on 60 cases of ACC, looking across the entire genomes for alterations that might be driving the disease. The key findings were:


  • ACC has a "quiet" genome with relatively few alterations compared to most tumor types. Although no cancer is simple to stop, simpler tumors may be targeted more effectively than complex tumors with "noisy" genomes.
  • As in prior studies, the oncogene MYB was altered in the majority of ACC cases, indicating its primary role in the disease. Secondary clusters of genetic alterations were identified that may facilitate the matching of targeted therapies to ACC patient subsets.
  • Chromatin regulators were mutated in 35% of ACC tumors, pointing to epigenetic disruptions in many cases. These genes handle the machinery of DNA packaging and expression.  
  • The FGF-IGF-PI3K pathway was altered in 30% of ACC tumors. These gene families are growth factors that often are implicated in cancer. 
  • The NOTCH pathway was altered in 13% of ACC tumors. This gene can act as both an oncogene and a tumor suppressor. 


The MSKCC study provides important context for ACC patients seeking improved treatments. Extensive efforts are under way to inhibit MYB directly with drugs, but they have yet to bear fruit. In the meantime, patients with progressive ACC may wish to consult with their physicians about tumor profiling to identify secondary genetic alterations. Each tumor will have its own blend of genetic alterations driving its progression. With this study, we now understand that subsets of ACC tumors are likely to include molecular targets related to MYB, chromatin regulators, FGF, IGF, PI3K and NOTCH. Fortunately, there is a growing list of drugs in development that inhibit these targets. Indeed, one of the current clinical trials for ACC patients inhibits the receptors of FGF.


The study was funded primarily by the National Institutes of Health (NIH), including the National Institute of Dental and Craniofacial Research (NIDCR). Dr. Chan and his colleagues are analyzing the tumors of an additional 50 ACC patients to depict further the landscape of ACC genomics. The MD Anderson Cancer Center, the Wellcome Trust Sanger Institute, Johns Hopkins University and TGEN also will be publishing DNA sequencing data soon, bringing the number of ACC cases with extensive genomic characterization to more than 200, a remarkably high number for a rare cancer. ACCRF has supported all these efforts.


Note: Patients should not confuse the terms "genetic" and "inherited". ACC, like all cancers, is viewed as a "genetic" disease in that altered genes lead to uncontrolled growth of previously-normal cells. However, ACC is not "inherited" because the genetic alterations are acquired during the patient's lifetime in one initiating cell, not handed down from parental DNA found in all cells. Some cancers are heavily influenced by heredity, but that is not the case with ACC. 


Clinical Trials: ASCO Abstracts and Open Studies


The energy and commitment of the ACC community is accelerating progress towards the clinic. In years past, there have been relatively few clinical trials reporting on the efficacy of systemic therapies (drugs) in ACC patients. However, at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting, there will be four abstracts describing preliminary data on novel drugs taken by ACC patients:


Dovitinib - The University of Virginia (Charlottesville, VA) reported that 2 of 19 patients that could be evaluated (11%) had a partial response (30% or greater tumor shrinkage) with Dovitinib, an inhibitor of FGFR and VEGFR. In addition, 15 of the 19 patients (79%) had stable disease; 9 of 13 patients with sufficient follow-up (69%) had stable disease for more than 6 months. This preliminary data suggests the highest efficacy of any systemic therapy in ACC to date.


Sorafenib - The Istitutio Nazionale dei Tumori (Milan, Italy) reported on a study of Sorafenib in 19 patients with ACC and 18 patients with other salivary gland cancers. Two of 19 ACC patients (11%) had a partial response. The abstract does not break out the rate of stable disease for ACC patients, but states that 21 of 37 salivary gland cancer patients (57%) had stable disease with a median duration of 7 months.


Vorinostat - The Karmanos Institute (Detroit, MI) reported on a study of 30 ACC patients treated with Vorinostat (also called SAHA). The drug is an inhibitor of HDAC, a family of genes involved in chromatin modifications. One patient (3%) had a partial response, while 25 (83%) had stable disease. Six patients (20%) did not progress for more than 1 year.


Dasatinib - The Medical College of Wisconsin (Milwaukee, WI) reported on a study of 40 patients with ACC and 14 patients with other salivary gland cancers who were treated with Dasatinib. Among the ACC patients, there were no partial responses and 21 (52%) had stable disease with a median duration of 4.8 months.


We anticipate further reports from ACC clinical trials over the coming months. Studies of Axitinib (MSKCC), Dovitinib (Seoul National University) and Sorafenib (Manchester Cancer Research Centre) have completed enrollment and a study of MK-2206 (MSKCC) has been suspended pending analysis of data from the first stage. New clinical trials are being planned for follow-on studies of some drugs mentioned above as well as additional novel agents. The ACC community may keep apprised of open studies on ACCRF's Current Studies webpage. And the results of other drugs are available on the Past Studies webpage.  


There remains a long road ahead to finding a cure for ACC. But patients are enrolling in well-designed trials of dedicated researchers and, together, they are narrowing down the drugs that will buy precious time. We look forward to better and quicker answers about how to improve treatments for ACC patients.


Friends of ACCRF: Patient Gathering & Fundraiser
2013 ACC Survivor Meeting
2013 ACC Survivor Meeting

On March 9th, over 40 ACC survivors and family members met in Needham, MA to socialize and connect with other ACC families.  We enjoyed learning about each person's hopes and fears, ate a delicious lunch, and listened to presentations from ACCOI (to learn about support for the ACC patient community) and ACCRF (to learn about current ACC research).  It was a wonderful afternoon spending time with such positive, supportive and very funny new friends!
2013 ACCRF Board Members
ACCRF Board of Directors
Jeff & Marnie Kaufman, Kara Gelb, Ralph Mollis & Douglas Meyer
That same evening, the 7th Annual Friends of ACCRF event drew a record 240 people and raised over $55,000!  In addition to a wide range of friends and family, this year's fundraiser attracted scores of patients and ACC researchers, who traveled from 10 states to be a part of the special evening. The event featured food, music, an auction and a lot of fun.  Most importantly, every dollar raised goes directly to support ACC research.


partnersFundraising Partners: Running to Raise Money for ACCRF
Wannabe race
Wannabe Cancer Free 5K

2012 NC 5K
NC Run for a Cure
Live Like Andi Run/Walk
Three recent races have raised over $45,000 to benefit ACCRF!

The 6th Annual Live Like Andi Run/Walk in MI, the 5th Annual PASO Race in Springfield, MA and the 1st Annual Wannabe Cancer Free 5K in Charlotte, NC. 

We are deeply grateful for the generous support.

Save the Date
Saturday, August 24, 2013
Dunn, NC
 Please Help Support ACC Research