You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1
Angela Toss
 -- 1782 2023-03-25 11:34:56 |
2 layout
Camila Xu
 Meta information modification 1782 2023-03-27 07:57:55 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Mastrodomenico, L.; Piombino, C.; Riccò, B.; Barbieri, E.; Venturelli, M.; Piacentini, F.; Dominici, M.; Cortesi, L.; Toss, A. Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer). Encyclopedia. Available online: https://encyclopedia.pub/entry/42536 (accessed on 20 July 2025).
Mastrodomenico L, Piombino C, Riccò B, Barbieri E, Venturelli M, Piacentini F, et al. Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer). Encyclopedia. Available at: https://encyclopedia.pub/entry/42536. Accessed July 20, 2025.
Mastrodomenico, Luciana, Claudia Piombino, Beatrice Riccò, Elena Barbieri, Marta Venturelli, Federico Piacentini, Massimo Dominici, Laura Cortesi, Angela Toss. "Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)" Encyclopedia, https://encyclopedia.pub/entry/42536 (accessed July 20, 2025).
Mastrodomenico, L., Piombino, C., Riccò, B., Barbieri, E., Venturelli, M., Piacentini, F., Dominici, M., Cortesi, L., & Toss, A. (2023, March 25). Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer). In Encyclopedia. https://encyclopedia.pub/entry/42536
Mastrodomenico, Luciana, et al. "Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)." Encyclopedia. Web. 25 March, 2023.
Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)
Edit
This entry is adapted from the peer-reviewed paper 10.3390/genes14030684

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant genetic disorder associated with an increased lifetime risk of developing colorectal cancer (CRC) (30–73%), endometrial carcinoma (EC) (30–51%) and, less frequently, other malignancies such as gastric, ovarian, urinary tract, pancreatic, small bowel, biliary tract, brain, and skin sebaceous cancers.

hereditary cancer syndromes MMR/MSI Lynch Syndrome HNPCC personalized therapy

1. Introduction

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant genetic disorder associated with an increased lifetime risk of developing colorectal cancer (CRC) (30–73%), endometrial carcinoma (EC) (30–51%) and, less frequently, other malignancies such as gastric, ovarian, urinary tract, pancreatic, small bowel, biliary tract, brain, and skin sebaceous cancers [1][2][3][4]. LS is due to germline PVs in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 or PMS2) or epithelial cell adhesion molecule (EPCAM, which causes epigenetic silencing of MSH2), which are crucial to correct DNA mismatches during DNA replication. The deficient MMR (dMMR) mechanism leads to the accumulation of frequent somatic mutational events in cancer-related genes containing tandemly repeated DNA motifs called microsatellites (Figure 1). The condition of genetic hypermutation due to impaired DNA MMR is called microsatellite instability (MSI).
Genes 14 00684 g002
Figure 1. Overview of microsatellite stability and instability mechanism and response to immunotherapy. When the DNA mismatch repair protein complex is intact, DNA replication errors are repaired. MSS tumors have a low neoantigen burden, therefore blockade of the PD-1-PD-L1 interaction through immune checkpoint inhibitors results in low T-cell activation against tumor cells. In MMR deficiency, failure in the elimination of the DNA replication error leads to a high number of somatic mutations and neoantigens. This results in a stronger anti-tumor immune response and sensitivity to the immune checkpoint blockade.

2. dMMR/MSI-H Colorectal Cancer Associated to Hereditary Predisposition

Due to its implications for prevention and treatments, tumor testing with immunohistochemistry for MMR proteins and/or MSI is recommended for every new CRC diagnosis [4][5]. It is important to underline that approximately 10% of CRCs display MLH1 loss of expression because of somatic hypermethylation of the MLH1 promoter, which is often associated with BRAF V600E PV in sporadic CRC. For this reason, methylation analysis of the MLH1 promoter in the tumor and/or analysis for somatic BRAF V600E PV should be carried out first to exclude LS [6]. Based on these findings, full germline genetic testing should be offered to every new MSI-H/dMMR cancer diagnosis—excluding those who show BRAF V600E somatic PV and/or hypermethylation of the MLH1 promoter—and to families who display high clinical risk [4].
It is noteworthy that in a proportion of patients with MSI/dMMR tumors, the somatic alteration is not associated with a germline PVs in MMR genes. This might be due to the presence of germline PVs in genes other than MMR that can mimic the LS phenotype. Particularly, germline PVs in the POLE/POLD1 proofreading domain cause polymerase proofreading-associated polyposis (PPAP), a dominant genetic disorder associated with an increased risk of CRC, EC and other malignancies with an ultra-mutated phenotype [7].

3. Chemotherapy

Historically, the role of dMMR is known as a negative predictor of response to treatment with fluoropyrimidines in selected subgroups of patients. Sargent et al., reported a detrimental role of the use of adjuvant 5-fluorouracil (5-FU) in stage II dMMR CRC patients [8]. On the contrary, patients with stage III dMMR CRC showed a statistically significant benefit from 5-FU adjuvant treatment [9]. As a consequence, MMR protein status assessment is recommended by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO) guidelines for patients with resected stage II CRC, since adjuvant chemotherapy may be avoided in dMMR individuals [4][10]. Furthermore, in the neoadjuvant setting, subgroup analysis of the FOxTROT trial suggested less benefit from neoadjuvant FOLFOX-based chemotherapy in dMMR patients [11].

4. Immune-Checkpoint Inhibitors

The dysfunctional MMR system causes 10 to 100 times as many somatic PVs compared to MMR proficient (pMMR) malignancies, which leads to the accumulation of many neoantigens (Figure 1) [12]. Moreover, dMMR cancers have a highly immunogenic tumor microenvironment with prominent lymphocyte infiltrates [13][14]. Based on this evidence, Le et al., hypothesized and demonstrated that dMMR tumors were more responsive to immune checkpoint blockade with pembrolizumab than those with pMMR [12]. The study was later expanded across 12 different dMMR tumor types, with 53% of objective radiographic responses (ORR) and 21% of complete responses (CR) [15]. Based on these findings, in 2017, the FDA granted accelerated approval for the use of the anti-PD-1 pembrolizumab for adult and pediatric patients with unresectable or metastatic dMMR/MSI-H solid tumors that have progressed after previous treatment, irrespective of tumor type, representing the first FDA approval agnostic of a cancer site. Subsequently, the clinical trials KEYNOTE-164 [16] and KEYNOTE-177 [17] confirmed the efficacy of pembrolizumab in advanced MSI-H/dMMR CRC in the second- and first-line setting, respectively. Moreover, based on the data from the CHECKMATE 142 study [18], the anti-PD-1 nivolumab gained FDA approval for the treatment of dMMR/MSI-H CRC that has progressed with regard to dMMR/MSI-H EC, in the phase 2 KEYNOTE-158 trial, pembrolizumab showed clinical benefit in patients with previously treated unresectable or metastatic non-colorectal MSI-H/dMMR cancer. Following these results, the FDA approved pembrolizumab for the treatment of patients with advanced MSI-H/dMMR EC who progressed following prior systemic therapy and are not candidates for curative surgery or radiation [19]. Based on the KEYNOTE-158 results, pembrolizumab was also approved for the treatment of gastric, small intestine and biliary tract cancers that have progressed on or following at least one prior therapy [19]. Other immune checkpoint inhibitors that have proven to be effective in dMMR EC include durvalumab [20], avelumab [21] and dostarlimab [22].
The phase I single-arm GARNET trial investigated the role of the anti-PD-1 monoclonal antibody dostarlimab in advanced solid tumors that have limited available treatment options. Interim data reported that dostarlimab is associated with durable antitumor activity and an acceptable safety profile for MSI-H/dMMR EC patients after prior platinum-based chemotherapy [22]. Based on these data, in 2021, dostarlimab gained FDA and EMA approval as a monotherapy for the treatment of recurrent or advanced MSI-H/dMMR ECs that have progressed after a platinum-containing regimen. Furthermore, dostarlimab recently met its primary endpoint of PFS in a planned interim analysis of the phase III RUBY trial of dostarlimab plus carboplatin-paclitaxel versus chemotherapy only in the first line setting in advanced or recurrent EC, both in the dMMR/MSI-H subgroup and in the overall population (NCT03981796, [23]).
Immune checkpoint inhibitors have also recently been tested in the resectable and locally advanced disease setting. A phase 2 study [24] investigated the activity of the anti-PD-1 monoclonal antibody dostarlimab in a cohort of 12 dMMR patients affected by stage II or III rectal adenocarcinoma. A clinical CR was shown in 100% of evaluable patients, resulting in the omission of the standard approach with chemoradiotherapy (CRT) and surgery. Furthermore, at the ESMO Congress 2022, Chalabi presented the preliminary results of the non-randomized phase 2 NICHE-2 study [25], in which 112 non-metastatic dMMR colon cancer patients received neoadjuvant treatment with nivolumab plus ipilimumab, showing a pathologic response rate of 99%, a major pathologic response rate of 95% and a pathologic CR rate of 67%. Considering the possible biological differences between Lynch- and non-Lynch-associated dMMR tumors, the pCR rate was assessed between these two groups. Among the 97 patients in the per protocol population for whom Lynch status was available, 32 had LS and experienced 78% of pCR compared to 58% in sporadic dMMR tumors. This result is consistent with evidence that LS-associated dMMR CRCs tend to exhibit stronger immunological reactions compared to sporadic dMMR tumors, due to the greater burden of somatic PVs, neoantigens and tumor infiltrating lymphocytes [26][27]. The 3-year disease-free survival data of the NICHE-2 study are expected in 2023. Of note, these unprecedented findings open the possibility of organ-preserving strategies in selected dMMR locally advanced CRCs.
The EMA-approved immune checkpoint inhibitors in dMMR/MSI-H tumors are summarized in Table 1.
Table 1. EMA-approved immune checkpoint inhibitors in dMMR/MSI-H malignancies (ICI: immune checkpoint inhibitor; CRC: colorectal cancer; EC: endometrial cancer; LS: Lynch Syndrome).
Cancer Type ICI EMA Indications Trial LS Patients Enrolled in the Trial
CRC Pembrolizumab As monotherapy in first-line treatment of metastatic CRC KEYNOTE-177 [17] Unknown
As monotherapy for unresectable or metastatic CRC after previous fluoropyrimidine-based combination therapy KEYNOTE-164 [16] Unknown
Nivolumab In combination with ipilimumab after prior fluoropyrimidine-based combination chemotherapy CheckMate 142 [18] 36%
EC Pembrolizumab As monotherapy for advanced or recurrent EC patients who have disease progression on or following prior treatment with platinum-containing therapy in any setting, and who are not candidates for curative surgery or radiation KEYNOTE-158 [19] Unknown
Dostarlimab As monotherapy for the treatment of recurrent or advanced EC that has progressed on or following prior treatment with a platinum-containing regimen GARNET [22] Unknown
Gastric, small intestine, biliary cancer Pembrolizumab As monotherapy for unresectable or metastatic disease patients who have progressed on or following at least one prior therapy KEYNOTE-158 [19] Unknown

5. Future Perspectives

Despite the impressive results obtained for neoadjuvant immune checkpoint inhibitors in dMMR CRC, validation in larger cohorts is awaited, and many questions still need to be answered. Future research on this topic should focus on identifying the best treatment regimen (monotherapy or combination), whether CRT and surgery should be omitted and if adjuvant treatment might be necessary. A randomized phase II/III clinical trial is currently assessing the efficacy of the anti-PD-1 sintilimab with or without CRT in patients with locally advanced rectal cancer in both dMMR and pMMR patients (NCT04304209). Similarly, a phase II single-arm study is investigating the efficacy of induction PD-1 blockade with dostarlimab in dMMR early stage rectal cancer patients (NCT04165772). In this trial, participants who exhibit clinical CR will proceed with a “watch and wait” strategy, whereas those who do not show clinical CR will receive standard CRT and surgery. Furthermore, the ongoing phase III MK-347 (NCT05173987) and DOMENICA (NCT05201547) trials are, respectively assessing the safety and efficacy of pembrolizumab and dostarlimab compared to carboplatin and paclitaxel in previously untreated dMMR EC. In addition, the phase III double-blind randomized placebo-controlled AtTEnd trial is evaluating the activity of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrent EC, including dMMR patients (NCT03603184).
Current research is also focusing on chemoprevention in LS patients. To date, no drug has been approved for this indication, and aspirin represents the only pharmacological therapy suggested for LS patients by the NCCN guidelines [10]. Current research aims to identify the optimal aspirin dose (CAPP-3 trial) and other potentially chemopreventive agents, such as progestins for EC prevention [28] and atorvastatin (NCT04379999), omega-3-acid ethyl esters (NCT03831698) and mesalamine (NCT04920149) for CRC prevention. The role of the anti-PD-1 tripleitriumab in preventing adenomatous polyps and second primary tumors in patients with LS is under evaluation in a randomized phase III trial (NCT04711434). Moreover, preclinical [29] and clinical [30] findings support the preventive role of neoantigen-based vaccines for LS-related cancers and have led to the development of two ongoing clinical trials (NCT05078866, NCT05419011).

References

  1. Lynch, H.T.; De la Chapelle, A. Hereditary colorectal cancer. N. Engl. J. Med. 2003, 348, 919–932.
  2. Engel, C.; Loeffler, M.; Steinke, V.; Rahner, N.; Holinski-Feder, E.; Dietmaier, W.; Schackert, H.K.; Goergens, H.; Doeberitz, M.V.K.; Goecke, T.O.; et al. Risks of Less Common Cancers in Proven Mutation Carriers with Lynch Syndrome. J. Clin. Oncol. 2012, 30, 4409–4415.
  3. Samadder, N.J.; Smith, K.R.; Wong, J.; Thomas, A.; Hanson, H.; Boucher, K.; Kopituch, C.; Cannon-Albright, L.A.; Burt, R.W.; Curtin, K. Cancer Risk in Families Fulfilling the Amsterdam Criteria for Lynch Syndrome. JAMA Oncol. 2017, 3, 1697.
  4. Stjepanovic, N.; Moreira, L.; Carneiro, F.; Balaguer, F.; Cervantes, A.; Balmaña, J.; Martinelli, E. Hereditary Gastrointestinal Cancers: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Ann. Oncol. 2019, 30, 1558–1571.
  5. Oaknin, A.; Bosse, T.J.; Creutzberg, C.L.; Giornelli, G.; Harter, P.; Joly, F.; Lorusso, D.; Marth, C.; Makker, V.; Mirza, M.R.; et al. Endometrial Cancer: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up. Ann. Oncol. 2022, 33, 860–877.
  6. Capper, D.; Voigt, A.; Bozukova, G.; Ahadova, A.; Kickingereder, P.; von Deimling, A.; von Knebel Doeberitz, M.; Kloor, M. BRAF V600E-Specific Immunohistochemistry for the Exclusion of Lynch Syndrome in MSI-H Colorectal Cancer: BRAF V600E Immunohistochemistry in MSI-H Colorectal Cancer. Int. J. Cancer 2013, 133, 1624–1630.
  7. Palles, C.; Cazier, J.-B.; Howarth, K.M.; Domingo, E.; Jones, A.M.; Broderick, P.; Kemp, Z.; Spain, S.L.; Guarino, E.; Salguero, I.; et al. Mutations Affecting the Proofreading Domains of POLE and POLD1 Predispose to Colorectal Adenomas and Carcinomas. Nat. Genet. 2013, 45, 136–144.
  8. Sargent, D.J.; Marsoni, S.; Monges, G.; Thibodeau, S.N.; Labianca, R.; Hamilton, S.R.; French, A.J.; Kabat, B.; Foster, N.R.; Torri, V.; et al. Defective Mismatch Repair as a Predictive Marker for Lack of Efficacy of Fluorouracil-Based Adjuvant Therapy in Colon Cancer. J. Clin. Oncol. 2010, 28, 3219–3226.
  9. Sinicrope, F.A.; Foster, N.R.; Thibodeau, S.N.; Marsoni, S.; Monges, G.; Labianca, R.; Yothers, G.; Allegra, C.; Moore, M.J.; Gallinger, S.; et al. DNA Mismatch Repair Status and Colon Cancer Recurrence and Survival in Clinical Trials of 5-Fluorouracil-Based Adjuvant Therapy. JNCI J. Natl. Cancer Inst. 2011, 103, 863–875.
  10. National Comprehensive Cancer Network Guidelines. Genetic/Familial High-Risk Assessment: Colorectal (Version 1.2022). Available online: https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf (accessed on 7 November 2022).
  11. Seligmann, J.F.; FOxTROT Collaborative Group. FOxTROT: Neoadjuvant FOLFOX Chemotherapy with or without Panitumumab (Pan) for Patients (Pts) with Locally Advanced Colon Cancer (CC). J. Clin. Oncol. 2020, 38 (Suppl. S15), 4013.
  12. Le, D.T.; Uram, J.N.; Wang, H.; Bartlett, B.R.; Kemberling, H.; Eyring, A.D.; Skora, A.D.; Luber, B.S.; Azad, N.S.; Laheru, D.; et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N. Engl. J. Med. 2015, 372, 2509–2520.
  13. Mlecnik, B.; Bindea, G.; Angell, H.K.; Maby, P.; Angelova, M.; Tougeron, D.; Church, S.E.; Lafontaine, L.; Fischer, M.; Fredriksen, T.; et al. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. Immunity 2016, 44, 698–711.
  14. Kloor, M.; von Knebel Doeberitz, M. The Immune Biology of Microsatellite-Unstable Cancer. Trends Cancer 2016, 2, 121–133.
  15. Le, D.T.; Durham, J.N.; Smith, K.N.; Wang, H.; Bartlett, B.R.; Aulakh, L.K.; Lu, S.; Kemberling, H.; Wilt, C.; Luber, B.S.; et al. Mismatch Repair Deficiency Predicts Response of Solid Tumors to PD-1 Blockade. Science 2017, 357, 409–413.
  16. Le, D.T.; Kim, T.W.; Van Cutsem, E.; Geva, R.; Jäger, D.; Hara, H.; Burge, M.; O’Neil, B.; Kavan, P.; Yoshino, T.; et al. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability–High/Mismatch Repair–Deficient Metastatic Colorectal Cancer: KEYNOTE-164. JCO 2020, 38, 11–19.
  17. André, T.; Shiu, K.-K.; Kim, T.W.; Jensen, B.V.; Jensen, L.H.; Punt, C.; Smith, D.; Garcia-Carbonero, R.; Benavides, M.; Gibbs, P.; et al. Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer. N. Engl. J. Med. 2020, 383, 2207–2218.
  18. Overman, M.J.; McDermott, R.; Leach, J.L.; Lonardi, S.; Lenz, H.-J.; Morse, M.A.; Desai, J.; Hill, A.; Axelson, M.; Moss, R.A.; et al. Nivolumab in Patients with Metastatic DNA Mismatch Repair-Deficient or Microsatellite Instability-High Colorectal Cancer (CheckMate 142): An Open-Label, Multicentre, Phase 2 Study. Lancet Oncol. 2017, 18, 1182–1191.
  19. Marabelle, A.; Le, D.T.; Ascierto, P.A.; Di Giacomo, A.M.; De Jesus-Acosta, A.; Delord, J.-P.; Geva, R.; Gottfried, M.; Penel, N.; Hansen, A.R.; et al. Efficacy of Pembrolizumab in Patients with Noncolorectal High Microsatellite Instability/Mismatch Repair–Deficient Cancer: Results from the Phase II KEYNOTE-158 Study. JCO 2020, 38, 1–10.
  20. Antill, Y.; Kok, P.S.; Stockler, M.R.; Robledo, K.; Yip, S.; Parry, M.; Smith, D.; Spurdle, A.; Barnes, E.; Friedlander, M.L.; et al. Updated Results of Activity of Durvalumab in Advanced Endometrial Cancer (AEC) According to Mismatch Repair (MMR) Status: The Phase II PHAEDRA Trial (ANZGOG1601). Ann. Oncol. 2019, 30, ix192.
  21. Konstantinopoulos, P.A.; Luo, W.; Liu, J.F.; Gulhan, D.C.; Krasner, C.; Ishizuka, J.J.; Gockley, A.A.; Buss, M.; Growdon, W.B.; Crowe, H.; et al. Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer. JCO 2019, 37, 2786–2794.
  22. Oaknin, A.; Tinker, A.V.; Gilbert, L.; Samouëlian, V.; Mathews, C.; Brown, J.; Barretina-Ginesta, M.-P.; Moreno, V.; Gravina, A.; Abdeddaim, C.; et al. Clinical Activity and Safety of the Anti–Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients with Recurrent or Advanced Mismatch Repair–Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. JAMA Oncol. 2020, 6, 1766.
  23. Mirza, M.R.; Coleman, R.L.; Hanker, L.C.; Slomovitz, B.M.; Valabrega, G.; Im, E.; Walker, M.; Guo, W.; Powell, M.A. ENGOT-EN6/NSGO-RUBY: A Phase III, Randomized, Double-Blind, Multicenter Study of Dostarlimab + Carboplatin-Paclitaxel versus Placebo + Carboplatin-Paclitaxel in Recurrent or Primary Advanced Endometrial Cancer (EC). JCO 2020, 38 (Suppl. S15), TPS6107.
  24. Cercek, A.; Lumish, M.; Sinopoli, J.; Weiss, J.; Shia, J.; Lamendola-Essel, M.; El Dika, I.H.; Segal, N.; Shcherba, M.; Sugarman, R.; et al. PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer. N. Engl. J. Med. 2022, 386, 2363–2376.
  25. Chalabi, M.; Verschoor, Y.L.; van den Berg, J.; Sikorska, K.; Beets, G.; Lent, A.V.; Grootscholten, M.C.; Aalbers, A.; Buller, N.; Marsman, H.; et al. LBA7 Neoadjuvant Immune Checkpoint Inhibition in Locally Advanced MMR-Deficient Colon Cancer: The NICHE-2 Study. Ann. Oncol. 2022, 33, S1389.
  26. Sinicrope, F.A. Lynch Syndrome–Associated Colorectal Cancer. N. Engl. J. Med. 2018, 379, 764–773.
  27. Liu, G.-C.; Liu, R.-Y.; Yan, J.-P.; An, X.; Jiang, W.; Ling, Y.-H.; Chen, J.-W.; Bei, J.-X.; Zuo, X.-Y.; Cai, M.-Y.; et al. The Heterogeneity Between Lynch-Associated and Sporadic MMR Deficiency in Colorectal Cancers. Gynecol. Oncol. 2018, 110, 975–984.
  28. Lu, K.H.; Loose, D.S.; Yates, M.S.; Nogueras-Gonzalez, G.M.; Munsell, M.F.; Chen, L.; Lynch, H.; Cornelison, T.; Boyd-Rogers, S.; Rubin, M.; et al. Prospective Multicenter Randomized Intermediate Biomarker Study of Oral Contraceptive versus Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome. Cancer Prev. Res. 2013, 6, 774–781.
  29. Gebert, J.; Gelincik, O.; Oezcan-Wahlbrink, M.; Marshall, J.D.; Hernandez-Sanchez, A.; Urban, K.; Long, M.; Cortes, E.; Tosti, E.; Katzenmaier, E.-M.; et al. Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity with Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model. Gastroenterology 2021, 161, 1288–1302.e13.
  30. Kloor, M.; Reuschenbach, M.; Pauligk, C.; Karbach, J.; Rafiyan, M.-R.; Al-Batran, S.-E.; Tariverdian, M.; Jäger, E.; von Knebel Doeberitz, M. A Frameshift Peptide Neoantigen-Based Vaccine for Mismatch Repair-Deficient Cancers: A Phase I/IIa Clinical Trial. Clin. Cancer Res. 2020, 26, 4503–4510.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Oncology; Genetics & Heredity
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Luciana Mastrodomenico
,
Claudia Piombino
,
Beatrice Riccò
,
Elena Barbieri
,
Marta Venturelli
,
Federico Piacentini
,
Massimo Dominici
,
Laura Cortesi
,
Angela Toss
View Times: 847
Revisions: 2 times (View History)
Update Date: 27 Mar 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Academic Video Service
    Feedback