One common factor could potentially explain the transition from MASLD to MASH to liver fibrosis to liver cancer: genetic biomarkers
A 2025 study analyzed the shared biomarkers across 3 conditions that are known precursors of liver cancer; metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis. Out of the 12,357 biomarkers known to be associated with liver cancer, the key ones shared between MASLD, MASH and liver fibrosis were found to be VEGFA, MMP9, PPARG, JUN, ESR1, and IGF1.
Important to note, while they are all biomarkers that appear to be tied to liver cancer, they don’t all influence disease progression in the same direction. Four of six were associated with poor patient outcomes when they were overly active: VEGFA, MMP9, PPARG and JUN. On the other hand, two of six were associated with poor patient outcomes when underactive: ESR1 and IGF1, meaning that at healthy levels these genes slow cancer progression, and at low levels they can’t do that effectively. In fact, the IGF1 biomarker specifically is thought to be a reliable reflection of liver disease progression; the lower the levels of IGF1, the more advanced the disease stage[1].
It is important to note that this research was conducted using a bioinformatics approach and further experimental research could be done to support these findings.
Citation:
Zhang, Chunye, et al. “Molecular mechanisms from the transition of MASLD-mash-liver fibrosis to liver cancer.” The Journal of Precision Medicine: Health and Disease, vol. 3, Oct. 2025, p. 100012, https://doi.org/10.1016/j.premed.2025.100012.
Researchers explore a potential new test type to detect biomarkers in those with non-small cell lung cancer
A study published in July 2025 looked into one biomarker in particular which is associated with non-small cell lung cancer: EGFR. As we know, biomarkers in the context of cancer are genes that differ in cancer tissue compared to healthy tissue. This gene can vary and mistakes can happen in more than one way; in the case of EGFR, its variants have been labelled p.L858R & p.E746_A750del. Not only does knowledge that someone has the EGFR biomarker inform treatment plans, but the plan can change based on what type of EGFR variant someone has. That goes to show how precise these genetic-informed treatment approaches really are!
Loop-Mediated Isothermal Amplification (LAMP) is a new diagnostic testing method to detect biomarkers variants such as the two listed above. The researchers compared this technique to current standard methods: NGS & PCR. The LAMP test generated results in under 1hr and was able to detect that someone had the p.L858R version of the EGFR biomarker with a 95.45% accuracy and the p.E746_A750del version with 100% accuracy.
Twenty healthcare professionals from 5 different countries completed a questionnaire and unanimously agreed that the LAMP test should be integrated as a first diagnostic tool. The arguments were that it reduces time, has lower equipment + testing costs, is portable and accelerates treatment decisions for patients.
Citation:
Clemente, C., Sequeira, M., Almeida, P., Carvalho, M., Aliyeva, E., Mehdizadeh, S., Aliyev, J., Melikova, L., & Flores, O. (2025). A rapid loop-mediated isothermal amplification (LAMP) test for the detection of somatic variants, P.L858R and p.E746_A750del, in non-small cell lung cancer patients: Comparison with real-time PCR and NGS. The Journal of Precision Medicine: Health and Disease, 2, 100005. https://doi.org/10.1016/j.premed.2025.100005
McGill’s MIPOGG tool acts as a guideline for clinicians to speed up the process of detecting cancer biomarkers in patients
McGill has developed what they called the McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) which can be used to guide health practitioners in determining whether or not a child with cancer should be tested for a cancer predisposition syndrome. This is another term used to describe hereditary cancer, where a gene passed down from a parent is what caused the cancer rather than it being acquired throughout someone’s lifetime[2]. Cancer predisposition syndromes account for around 10% of cancers; two frequent types include the breast-ovarian cancer syndrome and hereditary non-polyposis colon cancer[3].
The guidelines exist since 2019 as an app or web-based format and are now used in 70 countries across 6 continents. Based on the cancer and tumour type of the patient, there is an algorithm that will either immediately recommend a referral or guide the practitioner through a series of yes or no questions to determine whether a referral to genetic testing is required. After the recommendation has been made, the tool also offers educational modules specific to the individuals’ cancer type.
The study compared the performance of MIPOGG to routine clinical care as a measure of how it performed in cancer predisposition syndrome recognition. In terms of performance, the tool was as successful as health care providers at identifying individuals needing to be genetically tested at primary cancer diagnosis. As for patients who went on to develop a secondary tumour, MIPOGG was able to identify their need for testing faster than health care providers. In fact, it enabled earlier recognition of an inherited gene/biomarker in 410/412 children with cancer in phase I of the study. There were 9 patients who didn’t get diagnosed with a cancer predisposition syndrome by their practitioner until the second tumour arose whereas MIPOGG was able to identify it with the first tumour. Overall, the consensus is that this tool could improve patient outcomes by providing earlier answers to patients. It also standardizes the recommendations for the screening of hereditary cancer since factors such as tumour features, family history and practitioner experience among others can lead to variation in whose inherited cancer is identified.
Facts to keep in mind
- 1/10 children with cancer has a biomarker that’s been passed down from a parent
- There are 100+ types of cancers that children can be diagnosed with and 50+ cancer predisposition syndromes
- To diagnose a cancer predisposition syndrome a genetic test is required and a clinician to interpret it
Citation:
Goudie C, Witkowski L, Cullinan N, et al. Performance of the McGill Interactive Pediatric OncoGenetic Guidelines for Identifying Cancer Predisposition Syndromes. JAMA Oncol. 2021;7(12):1806–1814. doi:10.1001/jamaoncol.2021.4536
PARP inhibitor treatment may be better suited for those with BRCA2 mutations in comparison to BRCA1
Are PARP inhibitors more effective at treating one type of BRCA mutation over the other? Researchers looked into this, using information from patients with prostate cancer in the metastatic stage, for which castration was unsuccessful as a treatment approach.
PARP inhibitor treatment allows for cancer cells specifically to be targeted and killed, without damaging healthy cells. PARP, which is found inside cells, typically has a repair pathway in our body that the treatment (inhibitors) blocks. This way, the cancerous cells can’t get repaired through that pathway, so the body will recognize them as bad and get rid of them. There are currently two types of approved PARP inhibitors that are used for treatment: olaparib and rucaparib. These were used as well as two others: talazoparib and veliparib.
In this study that spanned across 12 academic centres, patients received one of the four PARP inhibitors between December 2014-July 2020. The main measure used in this study to track the effectiveness of the treatment was prostate-specific antigen levels, which you may know as PSA. Researchers took note of when these PSA levels dropped 50% after treatment, which would indicate that it was successful. Overall, 59% of patients had this 50% drop in PSA levels after PARP inhibitor treatment. With regard to the mutation types, patients with BRCA1 had fewer (23%) but faster PSA50 responses than patients with BRCA2 (63%).
The median amount of time it took for this treatment type to stop the prostate cancer progression was measured to be 40.7 and 43.4 weeks, using PSA levels and scans respectively to measure these values.
Relationship between BRCA 1/2 and other mutations
Stats were gathered for the number of people who had not only a BRCA (1 or 2) mutation but the TP53 mutation as well.
Prostate Cancer
Those with prostate cancer that had both BRCA gene and TP53 gene mutations.
BRCA1: 39% (19/49)
BRCA2: 22% (71/323)
Those with prostate cancer that had both BRCA gene and RB1 gene mutation.
BRCA1: 12% (6/49)
BRCA2: 30% (97/323).
Breast Cancer
Those with breast cancer that had both BRCA gene and TP53 mutations.
BRCA1: 50% (144/288)
BRCA2: 41% (143/350)
Regarding the number of patients who responded to treatment, there were 72/123 (BRCA1: 3, BRCA2: 69). The most reliable measurement was overall survival, it was 91.0 weeks, with it being shorter for those with BRCA1 (49.6 weeks) compared to BRCA2 mutations (104.6 weeks). The overall survival was also lower for those whose BRCA mutation was accompanied by a TP53 mutation, or for whom one copy of the gene had the mutation rather than both copies. Both of these are more prevalent in BRCA1 mutations, which could explain the decreased efficiency of the treatment.
Citation:
- Fadi Taza et al. Differential Activity of PARP Inhibitors in BRCA1– Versus BRCA2-Altered Metastatic Castration-Resistant Prostate Cancer. JCO Precis Oncol 5, 1200-1220(2021).
CITATIONS
[1]Kaseb, A. O., Morris, J. S., Hassan, M. M., Siddiqui, A. M., Lin, E., Xiao, L., Abdalla, E. K., Vauthey, J.-N., Aloia, T. A., Krishnan, S., & Abbruzzese, J. L. (2011). Clinical and prognostic implications of plasma insulin-like growth factor-1 and vascular endothelial growth factor in patients with hepatocellular carcinoma. Journal of Clinical Oncology, 29(29), 3892–3899. https://doi.org/10.1200/jco.2011.36.0636
[2] Cancer predisposition syndrome. St. Louis Children’s Hospital. (n.d.). https://www.stlouischildrens.org/conditions-treatments/cancer-predisposition-syndrome
[3] Cancer predisposition syndrome. St. Louis Children’s Hospital. (n.d.). https://www.stlouischildrens.org/conditions-treatments/cancer-predisposition-syndrome