News and updates

January 2025

The International Replication Repair Deficiency Consortium (IRRDC) is pleased to share a newly published study entitled “Frequency and Impact of Constitutional Mismatch Repair Deficiency in Patients With High-Grade Glioma, a Retrospective Analysis of 7 Years in Pakistan.”

Authored by IRRDC collaborators at Aga Khan University Hospital in Karachi, Pakistan, this study provides valuable insights into the prevalence and clinical implications of CMMRD in pediatric high-grade gliomas.

The study underscores the importance of genetic testing and surveillance, and highlights the urgent need for affordable, targeted protocols in low-resource settings.

Read the full article on JCO Global Oncology.  This article is Open Access and free to read.

November 2024

The RRD Consortium is proud to announce that Melyssa Aronson, genetic counsellor for the consortium, has received the prestigious Outstanding Service Award at the CGA-IGC Conference.

Created in 2021 to honor Dr. Ahnen’s legacy, this award recognizes significant contributions to the care of patients with gastrointestinal hereditary syndromes and to advancing the mission of CGA-IGC. Melyssa’s contributions to genetic counseling and her leadership within the field have made a lasting impact.

The consortium is grateful to have Melyssa as part of the team, and we congratulate her on this well-deserved recognition.

April 2024
We are thrilled to announce the publication of a new groundbreaking study titled The Clinical and Biological Landscape of Constitutional Mismatch Repair Deficiency: An IRRDC Cohort Study in The Lancet Oncology, authored by Ayse Ercan, Dr. Anirban Das, Dr. Uri Tabori, and over 130 international collaborators.

Incorporating data from 201 patients, this study shed light on the broad spectrum of clinical features associated with CMMRD. Furthermore, it uncovered the impact of certain variants in the mismatch repair genes associated with earlier cancer onset and poorer survival compared to others, underlining the importance of genotype-phenotype correlations in managing CMMRD.

We would like to thank all contributors, collaborators and participants for their involvement in this study. Thanks to everyone’s efforts, we are continuously learning more effective strategies for managing this syndrome.

April 2024
We are pleased to share our newest study in NPJ Precision Oncology, which presents a unique case of mismatch repair deficiency. This work, led by Dr. Victoria Forster and IRRDC collaborators and families, delves into the impact of biallelic EPCAM deletions on inducing tissue-specific replication repair deficiency and cancer predisposition.

By leveraging new iPSC and organoid technologies, this study emphasizes the importance of using cutting-edge cellular and molecular techniques to better understand tumor formation. In addition, it highlights the importance of understanding tissue-specific mechanisms in guiding our understanding of replication repair deficiency.

This research emphasizes the importance of continued research efforts in understanding MMRD its complexities. We extend our gratitude to the authors, family and collaborators for their important contributions.

November 2023
We are excited to share that our new paper on immunotherapy was nominated by the Canadian Cancer Immunotherapy Consortium (CCIC) for an oral presentation at the World Immunotherapy Council (WIC) for Young Investigators at SITC 2023. This nomination is in recognition of scientific excellence in the field of cancer immunotherapy.

October 2023
We are thrilled to share the release of a new research paper, spearheaded by Dr. Anirban Das in collaboration with an international team of IRRDC members.

Entitled “Combining Immunotherapies to Improve Outcomes in Replication Repair Deficient (RRD) High-Grade Gliomas that Don’t Respond to Anti-PD1 Monotherapy,” this paper highlights promising approaches for patients with tumors that don’t initially respond well to the standard treatment. Specifically, it reveals how combining immunotherapies after anti-PD1 monotherapy failure can significantly extend survival, particularly for those with a high mutation burden. This research unveils encouraging and delayed responses and emphasizes the importance of personalized treatment approaches.

To learn more, you can read the full article on Cancer Discovery. Please reach out to us directly at replication.repair@sickkids.ca if you have any questions!

February 2023
We are happy to announce that the talks from our third education series are now available to watch on our website and on YouTube.

This seminar featured two speakers, as well as a brief Q&A period following each presentation. The first talk was by Ayse Ercan who presented the results of her large study on phenotype-genotype relationships within our registry. The second talk was given by Dr. Liana Nobre who described a novel diagnostic tools currently in the process of clinical translation for monitoring and treating CMMRD.

The event closed with a 25-minute panel-discussion session addressing frequently asked questions we receive from patients.

Please visit our YouTube channel to view the entire seminar, or watch the individual talks from this seminar, and our previous two seminars, on our media page.

March 2022
The IRRDC is pleased to share our second newsletter, which highlights recent work that has advanced our understanding of immune-based therapies for patients with CMMRD. We welcome you to contact us regarding any questions, comments, or feedback. Enjoy!

Please click here to download the second issue

February 1, 2022
Congratulations to Dr. Das and the team! Our newest research recently published in Nature Medicine finds that immune-based therapy may help treat certain childhood cancers that are resistant to more common cancer treatments such as chemotherapy and radiation therapy. You can read more about this work here.

October 27th, 2021

We are very excited to announce that we have published the first issue of our inaugural newsletter which contains recent research highlights and articles written by members of our team and global family. We encourage you to share this newsletter with those you feel may be interested in our latest work.

Please click here to download the first issue

In addition, we would like to announce our second educational seminar which will be held virtually on November 30^th from 8-9am EST. Details can be found on our Eventbrite Page . If you are interested in attending this event, please register on Eventbrite. A link to the webinar will be provided the week before the event. For those who cannot attend live, the talks will be recorded and disseminated to those registered following the event.

October 21st, 2021

We would like to extend a huge congratulations to the incredible Yash Krishnan for his award nomination for “Federal or State Advocacy by a Teenager” through the EveryLife Foundation for Rare Diseases. This award honours teen advocates that have advocated for novel state or federal legislation

Yash and his family play an enormous role in our group as patient and parent advocates. They are dedicated to raising awareness and funding for CMMRD and other rare diseases by engaging with the FDA and international politicians. We are so grateful to have them as part of this team.

July 15, 2021
The talks from our very first education night (held on April 1st, 2021) are now available

Please follow this link to our Education Night page to see our inaugural talks, where Dr. Vanessa Bianchi discusses how following a surveillance protocol has greatly improved survival for individuals with CMMRD, and Dr. Victoria Forster discusses how we can use some CMMRD patient samples to generate “mini-organs” which may be used for a personalised medicine approach to patient care in the future.

May 5, 2021
Congratulations to Carol Durno, Ayse Bahar Ercan, Vanessa Bianchi, Uri Tabori and many additional collaborators from the RRD consortium for their landmark study on the efficacy of the surveillance protocol, now published in the Journal of Clinical Oncology.

Major findings from this study include:

1. Surveillance enables early tumour detection
   • 100% of GI and solid tumours, and 75% of brain tumours were identified asymptomatically in patients undergoing surveillance

2. Surveillance significantly improves long-term survival
   • Four-year survival was 79% for patients who adhered to the full protocol, in contrast to only 15% for patients not under surveillance. Strikingly, four-year survival was still 55% for patients who only had partial surveillance.

3. Low-grade tumors identified by surveillance have a high likelihood of transforming, emphasizing the need for early detection and resection.
   • 100% of low-grade tumors that were not resected transformed to high-grade within 6 years.

Ultimately, these results emphasise the momentous survival benefit of surveillance in patients with CMMRD.

Please visit the JCO Journal Page to read more about this study and download a copy of this paper.

March 2021
Congratulations to Melissa Galati and the rest of the IRRDC for their new publication in Cancer Discovery, showing that treatment of patients with RAS/MAPK hypermutant gliomas have durable responses to MEK inhibition.

You can read more about this paper on Cancer Discovery.