Rectum Cancer, AdenocarcinomaADAR1TNTNCT07108348
ADAR1 Expression Level in Rectal Cancer
An observational study of Rectum Cancer, Adenocarcinoma, run by Necmettin Erbakan University at 1 site in Turkey (Türkiye).
Trial summary
Total neoadjuvant therapy (TNT) is currently the standard treatment for locally/locally advanced rectal cancer due to better response and fewer distant metastases. In TNT, sequential chemotherapy (CT) and chemoradiotherapy (CRT) are planned and depending on the treatment response, either surgery is performed or a… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Rectum Cancer, Adenocarcinoma
- What is being tested?
- Adenosine deaminase acting on RNA1
- How many people
- 50 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Jun 2025to 1 Sep 2026
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients diagnosed with locally advanced rectal cancer who presented to the medical oncology, radiation oncology, and general surgery clinics of Necmettin Erbakan University Faculty of Medicine Hospital.
Who may be able to join
- Histological and staging diagnosis of local/locally advanced rectal cancer
- ECOG performance score between 0 and 2
- No contraindications for chemotherapy (CT) and/or radiotherapy (RT)
Who cannot join
- Those diagnosed with metastatic rectal cancer
- Those suspected of having rectal cancer or patients with a diagnosis of a second primary cancer
- Those who have not signed the informed consent form
- Those with contraindications for chemotherapy (CT) and/or radiation therapy (RT)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Necmettin Erbakan University Faculty of Medicine, Departmen of Medical Oncology
Konya, Meram, 42090
Mehmet Artaç, MD, +90 532 267 98 38, mehmetartac@yahoo.com
Ahmet Oruç, MD
About this study
Official title: The Effect of ADAR1 Expression Level on Total Neoadjuvant Treatment Response in Locally Advanced Rectal Cancer
Total neoadjuvant therapy (TNT) is currently the standard treatment for locally/locally advanced rectal cancer due to better response and fewer distant metastases. In TNT, sequential chemotherapy (CT) and chemoradiotherapy (CRT) are planned and depending on the treatment response, either surgery is performed or a watch and wait approach is applied. Depending on tumor localization and patient performance status, CT is planned as induction or consolidation. Most of the time, mFOLFOX6 and CAPOX are preferred as CT regimen. In proximal rectal cancer, surgery can be performed without CRT and only after CT. In locally/locally advanced rectal cancer, the aim is to avoid surgery as much as possible or to perform sphincter-sparing surgery if possible. Colonoscopy and pelvic MR at the time of diagnosis are the most important steps in staging, treatment selection and decision making. These two diagnostic methods should be repeated especially for watch and wait decision and for response evaluation after TNT.
ADAR 1 (Adenosine deaminase acting on RNA1) is an RNA editing enzyme that catalyzes the deamination of adenosine to inosine (A-to-I), a dynamic modification that can lead to a diverse transcriptome in a combinatorial manner. A defect in ADAR1-mediated RNA modification results in abnormal regulation of substrates that can affect phenotypic changes in cancer. This phenomenon of over-regulation is seen in many cancers such as colon, liver, lung, breast and esophageal cancers and in many cases promotes tumor progression. In studies, increased ADAR1 expression has been associated with lower survival and worse prognosis, especially in metastatic colon and gastric cancer. ADAR1 is also predicted to increase proliferation through both the AKT pathway and the mTOR pathway and therefore may be targeted in the near future.
Read more
ADAR1 expression is monitored by RNA-based real time PCR. In order to demonstrate increased expression, biopsies should be taken from the malignant tissue and the intact tissue of the patient and the biopsy should be stored under -80 C conditions immediately after biopsy to prevent RNA degradation. The tissue will not come into contact with nitrogen or formaldehyde.
In this study, sufficient biopsies from cancerous and intact tissue will be taken from patients with suspected rectal cancer, confirmed by pelvic MRI and consent for participation in the study, and fresh tissue will be stored at -80 C in the genetics laboratory. After the TNT plan is made by the investigators and the treatment is completed, both pelvic MRI and control rectoscopy will be performed for preoperative evaluation. Again, biopsies will be taken from diseased and healthy tissue and ADAR1 expression will be evaluated. The study is planned to include 50 participants and a period of one year is foreseen for tissue procurement/storage.
The investigators' aim in this study will be to determine whether ADAR1 expression level changes after TNT, whether this predicts clinical and pathological response, whether responses change according to the selected CT, whether there is a difference between CT induction-consolidation/RT short or long course, and the relationship between tumor DNA mismatch repair enzyme status and ADAR1 level. The investigators primary endpoint will be the effect of the change in ADAR1 expression level on the response after TNT (ORR). Secondary endpoints will be quality of life, recurrence-free survival (RFS) and overall survival (OS).
Read the detailed description
Colorectal cancer is the third most common cancer in both sexes, but it ranks second in mortality after lung cancer, with one in ten cancer deaths attributed to colorectal cancer. Total neoadjuvant therapy (TNT) is currently considered the standard of care for the treatment of locally advanced rectal cancer. In this approach, all non-surgical interventions, including multi-agent chemotherapy and concurrent chemoradiotherapy (CRT), are administered prior to surgical resection or the decision to opt for non-operative treatment. Accumulating evidence suggests that TNT improves survival in patients with locally advanced rectal cancer and is expected to reduce distant metastasis through systemic chemotherapy, thereby preventing the onset of micrometastases. TNT has also been associated with improved compliance, reduced toxicity, decreased need for and duration of ileostomy, and improved anal sphincter preservation rates following a watch-and-wait strategy, along with increased complete clinical response. Studies have shown that the rate of pCR in patients receiving TNT therapy is approximately 20-40%. Although numerous randomized controlled trials have evaluated different TNT strategies compared to standard KRT treatment in terms of KRT sequencing, systematic chemotherapy, radiotherapy modality, and TNT intensity, it is known that the TNT approach demonstrates superior survival benefit compared to adjuvant chemotherapy following neoadjuvant KRT. However, TNT theoretically offers several surgical advantages, including an increased likelihood of sphincter-preserving surgery and a reduced need for ileostomy; however, results across studies are inconsistent.
ADAR 1 (Adenosine deaminase acting on RNA1) catalyzes the C6 deamination of adenosine (A) to produce inosine (I) in RNA regions characterized by a double-stranded structure, a process known as adenosine deamination acting on RNA (ATIRE). This process is crucial for altering RNA structures and sequences in both coding and non-coding RNAs, influencing tumor characteristics, tumor stage, drug responses, and patient survival, thereby significantly contributing to cancer progression. The role of ADAR1 in promoting tumorigenesis via the ATIRE pathway is becoming increasingly evident in various cancers, including stomach cancer, esophageal squamous cell carcinoma, breast cancer, hepatocellular carcinoma, and CRC.
ADAR1, ADAR2, and ADAR3 are members of the ADAR family; while ADAR1 and ADAR2 are widely expressed, ADAR3 is primarily expressed in the brain and lacks catalytic activity. ADAR1 contains RNA-binding domains (RBDs) and Zα domains, whereas ADAR2 contains only RBDs. Zα domains enable ADAR1 to bind to newly synthesized RNA and inhibit the activation of pathogenic interferons (IFNs). ADAR1 has two isoforms: an IFN-inducible form (p150) and a constitutively expressed form (p110). It has been found that ADAR1-p110 reduces the chemotactic potential of melanoma cells and promotes immune exclusion . Loss of ADAR1 function results in unregulated RNA accumulation, which can be mistakenly recognized as foreign by RIG-I (Retinoic acid-inducible gene I), thereby triggering its activation and subsequent IFN response. Additionally, DNA released from damaged cells can activate the cGAS (GMP-AMP synthase)-STING (stimulator of interferon genes) pathway, leading to the production of type I IFNs through both pathways. The interaction between ADAR1 and the cGAS-STING and RIG-I pathways highlights a crucial balance in immune regulation. ADAR1's ability to interact with IFNs, regulate IFN production, and its complex roles in cancer therapy, along with its higher expression in MSI-H (microsatellite instability-high) patients, high TMB (tumor mutation burden), PD-1/PDL-1 levels, naive B cells, active memory CD4 T lymphocytes, and M1 macrophage cells, suggests its potential for modulating responses to cancer therapies. A potential mechanism has been proposed whereby increased ADAR1 expression in gastric cancer leads to proliferation and migration of various diseases through the mTOR/p70S6 kinase/S6 ribosomal protein pathway. To investigate the functional relationship between ADAR1 and mTOR signaling, the mTOR kinase inhibitor rapamycin was used to treat gastric cancer cells and observe its effects on ADAR1-overexpressed cell proliferation and migration. The results showed that ADAR1 overexpression significantly promoted cell proliferation and migration as expected, but these effects were significantly attenuated in cells treated with rapamycin. This suggests that rapamycin may block the effects of ADAR1 overexpression on gastric cancer cell growth and migration. These results indicate that the mTOR signaling pathway is important for ADAR1-mediated gastric cancer progression.
Recently, the effect of increased ADAR1 expression on survival in metastatic colon cancer was investigated. Both overall survival (OS) and relapse-free survival (RFS) were found to be significantly reduced in the group with increased ADAR1 expression; however, the study did not include patients with early-stage rectal cancer[20]. For all these reasons, the prognostic value of ADAR1 expression levels and/or changes in locally advanced rectal cancer patients for TNT response will be investigated.
- Conditions
- Rectum Cancer, Adenocarcinoma
- Being tested
- Adenosine deaminase acting on RNA1
- Keywords
- ADAR1, rectum cancer, TNT
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adenosine deaminase acting on RNA1Genetic
Previous studies have demonstrated that increased ADAR1 expression is associated with poor survival in gastric and metastatic colon cancer. In rectal cancer, however, the relationship between ADAR1 levels and TNT response in locally advanced disease has not been investigated. Another point is that ADAR1 can also be studied using immunohistochemistry; however, its sensitivity and specificity are low, so in our study, RNA will be isolated and analyzed using real-time PCR.
| Study group | Role | What they receive |
|---|---|---|
| 50 patients with locally advanced rectal adenocarcinoma scheduled for TNT. | Biopsies will be taken from these 50 patients at the time of diagnosis and after TNT. The relationship between ADAR1 expression levels and TNT response will be investigated. Receives: Genetic: Adenosine deaminase acting on RNA1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate according to RECIST 1.1
Evaluation of target lesions
Complete Response (CR):
Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR):
At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Progressive Disease (PD):
At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm.
Stable Disease (SD):
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: From enrollment to the end of treatment at 12 weeks
Secondary outcomes (2)
Recurrence free survival
Recurrence-free survival refers to the period of time after treatment when a patient remains free of tumor recurrence.
Measured: Disease-free survival is evaluated up to 120 months after the first documented progression or death from any cause (whichever comes first) following surgery or watch and wait decision after TNT.
Assessment of Quality of Life
Quality of life will be assessed using The European Organisation for Research and Treatment of Cancer (EORTC) quality of life (QLQ-C30) questionnaire, which consists of 30 items, every 3 months for 1 year. Higher scores on this quality of life scale are associated with better quality of life.
Measured: every 3 months for 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2025
- Study start1 Jun 2025
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Rectum Cancer, AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- Necmettin Erbakan University
- Sponsor type
- University, hospital or other
- Collaborators
- Turkish Society of Medical Oncology
- Responsible party
- Principal investigator, Mehmet Artac, Necmettin Erbakan University
- Investigators
- Mehmet Artaç, MD, Study director, Necmettin Erbakan University Faculty of Medicine, Department of Medical Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07108348
- Sponsor's protocol ID
- 24948/2025/5785
- Other IDs
- Turkish Society of Med. Onc.
- Acronym
- ADAR1TNT
- Status last verified
- Aug 2025
- First submitted
- 1 Jul 2025
- Last updated
- 7 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication
Publications
Wang Q, Li X, Qi R, Billiar T. RNA Editing, ADAR1, and the Innate Immune Response. Genes (Basel). 2017 Jan 18;8(1):41. doi: 10.3390/genes8010041.
PubMed 28106799Okugawa Y, Toiyama Y, Shigeyasu K, Yamamoto A, Shigemori T, Yin C, Ichikawa T, Yasuda H, Fujikawa H, Yoshiyama S, Hiro J, Ohi M, Araki T, Kusunoki M, Goel A. Enhanced AZIN1 RNA editing and overexpression of its regulatory enzyme ADAR1 are important prognostic biomarkers in gastric cancer. J Transl Med. 2018 Dec 18;16(1):366. doi: 10.1186/s12967-018-1740-z.
PubMed 30563560Shigeyasu K, Okugawa Y, Toden S, Miyoshi J, Toiyama Y, Nagasaka T, Takahashi N, Kusunoki M, Takayama T, Yamada Y, Fujiwara T, Chen L, Goel A. AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer. JCI Insight. 2018 Jun 21;3(12):e99976. doi: 10.1172/jci.insight.99976. eCollection 2018 Jun 21.
PubMed 29925690Chan TH, Lin CH, Qi L, Fei J, Li Y, Yong KJ, Liu M, Song Y, Chow RK, Ng VH, Yuan YF, Tenen DG, Guan XY, Chen L. A disrupted RNA editing balance mediated by ADARs (Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma. Gut. 2014 May;63(5):832-43. doi: 10.1136/gutjnl-2012-304037. Epub 2013 Jun 13.
PubMed 23766440Eisenberg E, Levanon EY. A-to-I RNA editing - immune protector and transcriptome diversifier. Nat Rev Genet. 2018 Aug;19(8):473-490. doi: 10.1038/s41576-018-0006-1.
PubMed 29692414Chua YJ, Barbachano Y, Cunningham D, Oates JR, Brown G, Wotherspoon A, Tait D, Massey A, Tebbutt NC, Chau I. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol. 2010 Mar;11(3):241-8. doi: 10.1016/S1470-2045(09)70381-X. Epub 2010 Jan 25.
PubMed 20106720Glynne-Jones R, Grainger J, Harrison M, Ostler P, Makris A. Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious? Br J Cancer. 2006 Feb 13;94(3):363-71. doi: 10.1038/sj.bjc.6602960.
PubMed 16465172Aref A, Abdalla A. Erratum: Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Induction or Consolidation Chemotherapy? J Clin Oncol. 2025 Mar;43(7):898. doi: 10.1200/JCO-25-00095. Epub 2025 Jan 24. No abstract available.
PubMed 39854654
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of ADAR1 Expression Level on Total Neoadjuvant Treatment Response in Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT07108348
- Acronym / sponsor ID
- ADAR1TNT / 24948/2025/5785
- Conditions
- Rectum Cancer, Adenocarcinoma
- Keywords
- ADAR1, rectum cancer, TNT
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Necmettin Erbakan UniversityUniversity, hospital or other
- Collaborators
- Turkish Society of Medical Oncology
- Study start
- 1 Jun 2025 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 7 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Total neoadjuvant therapy (TNT) is currently the standard treatment for locally/locally advanced rectal cancer due to better response and fewer distant metastases. In TNT, sequential chemotherapy (CT) and chemoradiotherapy (CRT) are planned and depending on the treatment response, either surgery is performed or a watch and wait approach is applied. Depending on tumor localization and patient performance status, CT is planned as induction or consolidation. Most of the time, mFOLFOX6 and CAPOX are preferred as CT regimen. In proximal rectal cancer, surgery can be performed without CRT and only after CT. In locally/locally advanced rectal cancer, the aim is to avoid surgery as much as possible or to perform sphincter-sparing surgery if possible. Colonoscopy and pelvic MR at the time of diagnosis are the most important steps in staging, treatment selection and decision making. These two diagnostic methods should be repeated especially for watch and wait decision and for response evaluation after TNT.
ADAR 1 (Adenosine deaminase acting on RNA1) is an RNA editing enzyme that catalyzes the deamination of adenosine to inosine (A-to-I), a dynamic modification that can lead to a diverse transcriptome in a combinatorial manner. A defect in ADAR1-mediated RNA modification results in abnormal regulation of substrates that can affect phenotypic changes in cancer. This phenomenon of over-regulation is seen in many cancers such as colon, liver, lung, breast and esophageal cancers and in many cases promotes tumor progression. In studies, increased ADAR1 expression has been associated with lower survival and worse prognosis, especially in metastatic colon and gastric cancer. ADAR1 is also predicted to increase proliferation through both the AKT pathway and the mTOR pathway and therefore may be targeted in the near future.
ADAR1 expression is monitored by RNA-based real time PCR. In order to demonstrate increased expression, biopsies should be taken from the malignant tissue and the intact tissue of the patient and the biopsy should be stored under -80 C conditions immediately after biopsy to prevent RNA degradation. The tissue will not come into contact with nitrogen or formaldehyde.
In this study, sufficient biopsies from cancerous and intact tissue will be taken from patients with suspected rectal cancer, confirmed by pelvic MRI and consent for participation in the study, and fresh tissue will be stored at -80 C in the genetics laboratory. After the TNT plan is made by the investigators and the treatment is completed, both pelvic MRI and control rectoscopy will be performed for preoperative evaluation. Again, biopsies will be taken from diseased and healthy tissue and ADAR1 expression will be evaluated. The study is planned to include 50 participants and a period of one year is foreseen for tissue procurement/storage.
The investigators' aim in this study will be to determine whether ADAR1 expression level changes after TNT, whether this predicts clinical and pathological response, whether responses change according to the selected CT, whether there is a difference between CT induction-consolidation/RT short or long course, and the relationship between tumor DNA mismatch repair enzyme status and ADAR1 level. The investigators primary endpoint will be the effect of the change in ADAR1 expression level on the response after TNT (ORR). Secondary endpoints will be quality of life, recurrence-free survival (RFS) and overall survival (OS).
Detailed description
Colorectal cancer is the third most common cancer in both sexes, but it ranks second in mortality after lung cancer, with one in ten cancer deaths attributed to colorectal cancer. Total neoadjuvant therapy (TNT) is currently considered the standard of care for the treatment of locally advanced rectal cancer. In this approach, all non-surgical interventions, including multi-agent chemotherapy and concurrent chemoradiotherapy (CRT), are administered prior to surgical resection or the decision to opt for non-operative treatment. Accumulating evidence suggests that TNT improves survival in patients with locally advanced rectal cancer and is expected to reduce distant metastasis through systemic chemotherapy, thereby preventing the onset of micrometastases. TNT has also been associated with improved compliance, reduced toxicity, decreased need for and duration of ileostomy, and improved anal sphincter preservation rates following a watch-and-wait strategy, along with increased complete clinical response. Studies have shown that the rate of pCR in patients receiving TNT therapy is approximately 20-40%. Although numerous randomized controlled trials have evaluated different TNT strategies compared to standard KRT treatment in terms of KRT sequencing, systematic chemotherapy, radiotherapy modality, and TNT intensity, it is known that the TNT approach demonstrates superior survival benefit compared to adjuvant chemotherapy following neoadjuvant KRT. However, TNT theoretically offers several surgical advantages, including an increased likelihood of sphincter-preserving surgery and a reduced need for ileostomy; however, results across studies are inconsistent.
ADAR 1 (Adenosine deaminase acting on RNA1) catalyzes the C6 deamination of adenosine (A) to produce inosine (I) in RNA regions characterized by a double-stranded structure, a process known as adenosine deamination acting on RNA (ATIRE). This process is crucial for altering RNA structures and sequences in both coding and non-coding RNAs, influencing tumor characteristics, tumor stage, drug responses, and patient survival, thereby significantly contributing to cancer progression. The role of ADAR1 in promoting tumorigenesis via the ATIRE pathway is becoming increasingly evident in various cancers, including stomach cancer, esophageal squamous cell carcinoma, breast cancer, hepatocellular carcinoma, and CRC.
ADAR1, ADAR2, and ADAR3 are members of the ADAR family; while ADAR1 and ADAR2 are widely expressed, ADAR3 is primarily expressed in the brain and lacks catalytic activity. ADAR1 contains RNA-binding domains (RBDs) and Zα domains, whereas ADAR2 contains only RBDs. Zα domains enable ADAR1 to bind to newly synthesized RNA and inhibit the activation of pathogenic interferons (IFNs). ADAR1 has two isoforms: an IFN-inducible form (p150) and a constitutively expressed form (p110). It has been found that ADAR1-p110 reduces the chemotactic potential of melanoma cells and promotes immune exclusion . Loss of ADAR1 function results in unregulated RNA accumulation, which can be mistakenly recognized as foreign by RIG-I (Retinoic acid-inducible gene I), thereby triggering its activation and subsequent IFN response. Additionally, DNA released from damaged cells can activate the cGAS (GMP-AMP synthase)-STING (stimulator of interferon genes) pathway, leading to the production of type I IFNs through both pathways. The interaction between ADAR1 and the cGAS-STING and RIG-I pathways highlights a crucial balance in immune regulation. ADAR1's ability to interact with IFNs, regulate IFN production, and its complex roles in cancer therapy, along with its higher expression in MSI-H (microsatellite instability-high) patients, high TMB (tumor mutation burden), PD-1/PDL-1 levels, naive B cells, active memory CD4 T lymphocytes, and M1 macrophage cells, suggests its potential for modulating responses to cancer therapies. A potential mechanism has been proposed whereby increased ADAR1 expression in gastric cancer leads to proliferation and migration of various diseases through the mTOR/p70S6 kinase/S6 ribosomal protein pathway. To investigate the functional relationship between ADAR1 and mTOR signaling, the mTOR kinase inhibitor rapamycin was used to treat gastric cancer cells and observe its effects on ADAR1-overexpressed cell proliferation and migration. The results showed that ADAR1 overexpression significantly promoted cell proliferation and migration as expected, but these effects were significantly attenuated in cells treated with rapamycin. This suggests that rapamycin may block the effects of ADAR1 overexpression on gastric cancer cell growth and migration. These results indicate that the mTOR signaling pathway is important for ADAR1-mediated gastric cancer progression.
Recently, the effect of increased ADAR1 expression on survival in metastatic colon cancer was investigated. Both overall survival (OS) and relapse-free survival (RFS) were found to be significantly reduced in the group with increased ADAR1 expression; however, the study did not include patients with early-stage rectal cancer[20]. For all these reasons, the prognostic value of ADAR1 expression levels and/or changes in locally advanced rectal cancer patients for TNT response will be investigated.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 50 patients with locally advanced rectal adenocarcinoma scheduled for TNT. | – | Genetic: Adenosine deaminase acting on RNA1Biopsies will be taken from these 50 patients at the time of diagnosis and after TNT. The relationship between ADAR1 expression levels and TNT response will be investigated. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients diagnosed with locally advanced rectal cancer who presented to the medical oncology, radiation oncology, and general surgery clinics of Necmettin Erbakan University Faculty of Medicine Hospital.
Key inclusion criteria (3 listed)
- Histological and staging diagnosis of local/locally advanced rectal cancer
- ECOG performance score between 0 and 2
- No contraindications for chemotherapy (CT) and/or radiotherapy (RT)
Key exclusion criteria (4 listed)
- Those diagnosed with metastatic rectal cancer
- Those suspected of having rectal cancer or patients with a diagnosis of a second primary cancer
- Those who have not signed the informed consent form
- Those with contraindications for chemotherapy (CT) and/or radiation therapy (RT)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adenosine deaminase acting on RNA1Previous studies have demonstrated that increased ADAR1 expression is associated with poor survival in gastric and metastatic colon cancer. In rectal cancer, however, the relationship between ADAR1 levels and TNT response in locally advanced disease has not been investigated. Another point is that ADAR1 can also be studied using immunohistochemistry; however, its sensitivity and specificity are low, so in our study, RNA will be isolated and analyzed using real-time PCR. | Genetic | 50 patients with locally advanced rectal adenocarcinoma scheduled for TNT. |
Primary outcome
Objective response rate according to RECIST 1.1
Time frame: From enrollment to the end of treatment at 12 weeks
Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
2 secondary outcomes
Recurrence free survival
Time frame: Disease-free survival is evaluated up to 120 months after the first documented progression or death from any cause (whichever comes first) following surgery or watch and wait decision after TNT.
Assessment of Quality of Life
Time frame: every 3 months for 1 year.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Results publication: PubMed 28106799Wang Q, Li X, Qi R, Billiar T. RNA Editing, ADAR1, and the Innate Immune Response. Genes (Basel). 2017 Jan 18;8(1):41. doi: 10.3390/genes8010041.
- Results publication: PubMed 30563560Okugawa Y, Toiyama Y, Shigeyasu K, Yamamoto A, Shigemori T, Yin C, Ichikawa T, Yasuda H, Fujikawa H, Yoshiyama S, Hiro J, Ohi M, Araki T, Kusunoki M, Goel A. Enhanced AZIN1 RNA editing and overexpression of its regulatory enzyme ADAR1 are important prognostic biomarkers in gastric cancer. J Transl Med. 2018 Dec 18;16(1):366. doi: 10.1186/s12967-018-1740-z.
- Results publication: PubMed 29925690Shigeyasu K, Okugawa Y, Toden S, Miyoshi J, Toiyama Y, Nagasaka T, Takahashi N, Kusunoki M, Takayama T, Yamada Y, Fujiwara T, Chen L, Goel A. AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer. JCI Insight. 2018 Jun 21;3(12):e99976. doi: 10.1172/jci.insight.99976. eCollection 2018 Jun 21.
- Results publication: PubMed 23766440Chan TH, Lin CH, Qi L, Fei J, Li Y, Yong KJ, Liu M, Song Y, Chow RK, Ng VH, Yuan YF, Tenen DG, Guan XY, Chen L. A disrupted RNA editing balance mediated by ADARs (Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma. Gut. 2014 May;63(5):832-43. doi: 10.1136/gutjnl-2012-304037. Epub 2013 Jun 13.
- Results publication: PubMed 29692414Eisenberg E, Levanon EY. A-to-I RNA editing - immune protector and transcriptome diversifier. Nat Rev Genet. 2018 Aug;19(8):473-490. doi: 10.1038/s41576-018-0006-1.
- Results publication: PubMed 20106720Chua YJ, Barbachano Y, Cunningham D, Oates JR, Brown G, Wotherspoon A, Tait D, Massey A, Tebbutt NC, Chau I. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol. 2010 Mar;11(3):241-8. doi: 10.1016/S1470-2045(09)70381-X. Epub 2010 Jan 25.
- Results publication: PubMed 16465172Glynne-Jones R, Grainger J, Harrison M, Ostler P, Makris A. Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious? Br J Cancer. 2006 Feb 13;94(3):363-71. doi: 10.1038/sj.bjc.6602960.
- Results publication: PubMed 39854654Aref A, Abdalla A. Erratum: Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Induction or Consolidation Chemotherapy? J Clin Oncol. 2025 Mar;43(7):898. doi: 10.1200/JCO-25-00095. Epub 2025 Jan 24. No abstract available.
- ADAR1 in colon cancerLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mehmet Artaç, MD study director
Necmettin Erbakan University Faculty of Medicine, Department of Medical Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rectum Cancer, Adenocarcinoma, run by Necmettin Erbakan University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ahmet Oruç, MD (+90 0505 704 50 20, mdahmetoruc@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate according to RECIST 1.1 (time frame: From enrollment to the end of treatment at 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07108348, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.