Author: Lynch Syndrome Ireland

Using Only Immunotherapy Successfully Treats Several Cancers With MMRd Mutation, Improves Quality of Life

Immunotherapy drugs work by helping the immune system find and attack cancer cells. They work best when the cells are easier for the immune system to find.

Cancer cells that are MMRd look more foreign to the immune system. That makes them easier for immune cells to find. The checkpoint inhibitor drugs are more likely to work.

This therapy “unmasks” tumor cells, making it easier for the patient’s own immune system to recognise and kill cancer cells.

The treatment has proved particularly helpful for people whose tumors are caused by Lynch syndrome, an inherited condition that makes people much more likely to develop colorectal and other cancers.

“People with Lynch syndrome usually don’t respond well to chemotherapy, so this gives them an important new option for treatment of early-stage disease,” says Dr. Cercek.

https://www.mskcc.org/news/using-only-immunotherapy-successfully-treats-several-cancers-with-mmrd-mutation-improves-quality-of-life?utm_source=X&utm_medium=Organic+Social&utm_term=&utm_content=Image+of+Dr.+Cercek&utm_campaign=Social+Media+Posts+April+2025

Getting the CMMRD Facts Straight After Family Loses 3 Children in 6 Years to Hereditary Cancer Syndrome

Originally published February 29, 2016

Lynch syndrome is an autosomal dominant condition. This means that a person who carries one copy of a mutation in any of the genes known to cause Lynch syndrome is at increased risk to develop multiple adult-onset cancers, especially those of the colon, uterus, and ovaries.

A person who carries two mutations in the same gene in any of the genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2) has a completely different syndrome called Constitutional Mismatch Repair Deficiency (CMMRD). This usually occurs when a person inherits one mutation from their father and the other from their mother. This rare condition is associated with a high risk of early-onset cancers, including childhood onset cancers of the brain and blood. Café au lait spots, flat light-brown birthmarks on the skin, are also common.

https://www.mygenecounsel.com/getting-the-cmmrd-facts-straight/

Colorectal Cancer (Bowel Cancer) Risk Factors & Prevention

Certain inherited genetic syndromes: 

About 5–10% of people who develop colorectal cancer have inherited changes (mutations) in their genes (the functional units of our genetic material, also known as DNA) that can lead to them getting the disease. These are often associated with people having colorectal cancer at a younger age than average. The most common hereditary conditions leading to colorectal cancer are:

  • Lynch syndrome: This is the most common hereditary syndrome leading to colorectal cancer. It accounts for about 3–5% of all colorectal cancers. The lifetime risk of colorectal cancer in people with this condition is 20–70%.
Colorectal cancer: risk factors

Nous-209 off-the-shelf neoantigen immunotherapy induces robust neoantigen T cell response with the potential to intercept cancer in Lynch syndrome carriers 

Cancer interception represents a new approach, aimed at targeting precancerous lesions and therefore preventing cancer occurrence. Lynch syndrome is one of the most prevalent hereditary cancer syndromes, with an estimated prevalence of one in 300, and high-risk predisposition to several types of cancer, with up to 80% lifetime risk to develop CRC.

Loss of MMR proteins causes an accumulation of mutations in the microsatellite sequences, known as Microsatellite instability (MSI), that can lead to shared frameshift mutations .

Nous-209 is a neoantigen directed immunotherapy encoding 209 FSP shared across sporadic and hereditary MSI tumors and precancer lesions in clinical development for interception and treatment of MSI tumors (Leoni et al., 2020; NCT04041310).

Reported are the full set of safety and immunogenicity results of a Phase Ib/II study of Nous-209 monotherapy in LS carriers. (45 enrolled) Neoantigen specific immune responses post Nous-209 were observed in 100% of evaluable participants (37/37)

The complete safety and immunogenicity results from this Phase Ib/II trial support the further development of Nous-209 monotherapy, highlighting its potential to efficiently stimulate the immune system and intercept cancer in LS carriers.

https://aacrjournals.org/cancerres/article/85/8_Supplement_1/6427/758888/Abstract-6427-Nous-209-off-the-shelf-neoantigen

‘Phenomenal’ – study hailed a significant milestone in child cancer care

Professor Owen Smith, Consultant Paediatric Haematologist at Children’s Health Ireland (CHI), has launched Ireland’s first clinical study of genomics approaches in cancer care.

Genomic sequencing allows medical teams to better identify cancerous cells and target them specifically.

“We need to stop carpet bombing cancers and go for a more sniper fire or precision way of killing the cancer and reducing the side effects to the patient,” Prof Smith said.

“Genomic sequencing of the cancer and the patient will allow us to define the patients where chemotherapy can be safely reduced,”

The primary objective of MAGIC-I is to evaluate the clinical and health economic impact of implementing genomic diagnostics in paediatric cancer care in Ireland.

https://www.rte.ie/news/health/2025/0423/1508973-cancer-study/#:~:text=’Phenomenal’%20%2D%20study%20hailed%20a%20significant%20milestone%20in%20child%20cancer%20care&text=A%20five%2Dyear%20project%20using,according%20to%20a%20paediatric%20consultant.

Lynch Syndrome

https://www.cancer.ie/cancer-information-and-support/cancer-information/about-cancer/causes-of-cancer/cancer-and-genes/lynch-syndrome

Lynch syndrome increases the risk of a number of cancers. In general, the risk is highest for colorectal (bowel) cancer, but it depends on the gene affected. 

Some colorectal (bowel) cancers are hereditary. Up to 5 people out of every 100 diagnosed with bowel cancer have Lynch syndrome. Other cancers linked to Lynch syndrome include:

https://www2.hse.ie/conditions/lynch-syndrome/

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  4. Help and support
  5. Reducing your risk of cancer
  6. Children and family planning

Metachronous colorectal cancer risks after extended or segmental resection in MLH1, MSH2, and MSH6Lynch syndrome: multicentre study from the Prospective Lynch Syndrome Database

According to the European Hereditary Tumour Group’s latest position report, LS is now considered an umbrella term for four distinct types of LS: MLH1 syndrome, MSH2syndrome, MSH6 syndrome, and PMS2 syndrome. These syndromes vary with regard to the age of onset of the associated cancers, sex predominance, and cancer incidence rates.

PLSD: Analysis of 8500 path_MMR carriers undergoing colonoscopic surveillance .

The aim of this study was to prospectively evaluate the risk of metachronous CRC, stratified by gene and the extent of the resection in previous surgery, contributing to the ongoing discussion on surgical strategies for LS patients.

https://academic.oup.com/bjs/article/112/4/znaf061/8113421?login=false&fbclid=IwY2xjawJwP6BleHRuA2FlbQIxMAABHstJO1twd022mBrfrcrADPLF_LfJZU6EJp7fqx9eDmpDHwkEOS6dzNDs9AkU_aem_PKKQVZ4ubPhaO9VyxUkRzw

Bowel Prep for Colonoscopy: Quality Matters

Bowel Prep Is Critical

When we talk about quality in colonoscopy, we’re referring to adenoma detection and sessile serrated lesion detection, along with the associated documentation that we perform. 

Achieving that level of quality is not just about writing a prescription for the prep and instructing your patients to follow through with it. Rather, it means providing guidance around diet modification and medication management and explaining the importance of the prep and how it is integral to colonoscopy performance.

It’s a shared responsibility. You, as well as your staff, need to take the time to discuss it with your patients.

Ensuring a quality prep is central to achieving our overall goals in colonoscopy and also in colorectal cancer prevention. Quality is what the patient should expect when a prep is prescribed. Referring physicians and healthcare providers should expect their patients to receive a high-quality colonoscopy prep. It’s our obligation as gastroenterologists to fulfill these expectations. 

https://www.medscape.com/viewarticle/bowel-prep-colonoscopy-quality-matters-2025a10007al?form=login