RET rearrangement

Future research should further elucidate the complex interplay between these two diseases to prevent the transformation of HT into PTC and offer more personalized treatment plans for PTC patients, including considerations for preoperative thyroidectomy and lymph node dissection strategies, as well as postoperative TSH suppression therapy risk assessment. This review underscores the importance of a deeper understanding of HT and PTC interactions and offers new perspectives for future research directions and therapeutic strategies.

P2, N=125, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

The outcome of B-ALL with t(14;18)(q32;q21) is poor. Incorporating immune-therapies, chimeric antigen receptor (CAR)-T cell therapy, with or without HSCT, into the treatment regimens, might further improve outcomes.

P1/2, N=610, Recruiting, DualityBio Inc. | N=450 --> 610

This study underscores the importance of structural insights for developing targeted therapies against RET fusion-driven cancers and highlights the need for further investigation into complex RET fusion mechanisms to better understand RET-driven oncogenesis.

Our results implicate the first germline variant in RET in a family with NMTC as well as the first germline variants in PTGIR, GALNT10, and UBN1 in TC.

P=N/A, N=10000, Not yet recruiting, Henan Cancer Hospital; Henan Cancer Hospital

Two highly potent and selective RET small-molecule inhibitors, selpercatinib and pralsetinib, were granted accelerated approval for advanced RET fusion-positive NSCLC by the US Food and Drug Administration, and have been shown to be highly effective both in treatment-naive and previously treated patients with NSCLC. Selpercatinib has shown superiority over chemotherapy in a phase 3 study (LIBRETTO-431) in previously untreated patients with RET fusion-positive NSCLC, which established its place as the standard of care in this patient population. This review discusses the biology and clinical characteristics of RET-rearranged NSCLC and summarizes the evolution of treatment strategies, current understanding of mechanisms of resistance, and development of new-generation agents to overcome resistance.

This study emphasizes the crucial role of clinicogenomic repositories in advancing precision oncology across diverse populations, underscoring the utility of integrating clinical and genomic data in national repositories.

In this review, we discuss the targeted therapies available in France and the promising future molecules for managing rare oncogenic drivers. Targeted therapies have already proven their efficacy as first-line treatments for ROS-1 and RET alterations, and as second-line treatments for MET and BRAF mutations.

P1/2, N=168, Recruiting, AP Biosciences Inc. | Not yet recruiting --> Recruiting

This case highlighted potential application of Pralsetinib in locally advanced RET-positive NSCLC to prime surgical resection. Postoperative Pralsetinib adjuvant therapy should also be considered.

P2, N=20, Completed, Washington University School of Medicine | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Feb 2025

We presented the first case of cervical spindle cell neoplasm with TFG-NTRK3 gene rearrangement and retrieved 22 cases of NTRK rearranged spindle cell neoplasm of the uterine cervix from literature. The most prevalent type of gene fusion was TPM3-NTRK1, and almost all cases demonstrated S-100 and CD34 positivity by IHC. Surgery remains the initial treatment of choice and tyrosine receptor kinase (TRK) inhibitors may serve as a promising target therapy for patients with recurred or metastatic disease.

No abstract available

Here, we describe a case who has response to 40 mg of selpercatinib every other day because the dose had to be adjusted owing to adverse events such as liver dysfunction. Dose modification of selpercatinib, according to adverse event incidences, may be considered, as selpercatinib may be effective in some cases even at very low concentrations.

This study highlights CBF-AML heterogeneity and challenges established prognostic markers, suggesting a need for risk stratification reassessment, treatment strategy optimization, ELN guidelines implementation, and continuous molecular monitoring.

P2, N=20, Active, not recruiting, Washington University School of Medicine | Trial completion date: Dec 2024 --> Dec 2025

Combination therapy targeting RET and ROS1 using pralsetinib and lorlatinib achieved a partial response with limited durability of only four months. This is the first reported case of a RET fusion as a potential mechanism of resistance to lorlatinib, it identifies a novel RET fusion partner, and it emphasizes the importance of testing for acquired resistance mutations with both DNA and RNA at the time of progression in patients with targetable oncogenic drivers.

Our results support the utility of ctDNA assays concurrently with tissue testing for detection of translocations, with opportunities to further optimize performance.

P2, N=88, Recruiting, SWOG Cancer Research Network | Trial completion date: May 2029 --> May 2028

In contrast, rwRFS significantly improved for patients without common mutations (HR 0.342, 95 % CI 0.203 - 0.577, p< 0.001). These findings suggest that consolidation durvalumab may not be beneficial for patients with common driver mutations, underscoring the need for personalized treatment strategies in this population.

PE cfDNA genotyping has clinical applicability for NSCLC patients and can serve as an additional source for molecular testing. Incorporating PE NGS cfDNA analysis into genetic testing enhances diagnostic yield and aids in identifying actionable mutations in clinical practice.

P1, N=36, Recruiting, Transgene | Trial completion date: Mar 2025 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

P1/2, N=450, Recruiting, DualityBio Inc. | N=280 --> 450 | Trial completion date: Apr 2025 --> Sep 2026 | Trial primary completion date: Apr 2025 --> Sep 2026

Therefore, a good understanding regarding the genetic and epigenetic modifications is not only essential for the diagnosis and prognosis of TC, but also for the development of novel therapeutics. In this review, most of the major TC-related genetic and epigenetic modifications and their potential as biomarkers for TC diagnosis and prognosis have been extensively discussed.

Most treatment-emergent adverse events were mild-to-moderate in severity. The study closed before the planned number of patients were enrolled in all cohorts. Sitravatinib had a manageable safety profile with modest signals of clinical activity in patients with molecularly selected solid tumors.Clinical trial registration: www.clinicaltrials.gov identifier is NCT02219711.

It is feasible to yield actionable molecular testing results from cytology specimens within 2 to 3 hours of the patient's diagnostic procedure, and aspirate smears can be triaged for this use at the time of the rapid on-site evaluation. Targetable genetic alterations can be detected from destained cytology aspirate smear slides and unstained FFPE cell blocks with high accuracy, precision, and analytical sensitivity and specificity. The cost of each cartridge ranges from $127 to $462 and is covered by the average national reimbursement schemes.

The AVENIO CGP Assay demonstrated high agreement with 2 established CGP tests, F1CDx and PGDx, in variant reporting, and closely aligned with F1CDx in HRDsig analysis across various tissue types. These results highlight the assay's reliability and demonstrate its utility in translational research.

P1, N=388, Recruiting, Shanghai Chest Hospital; CSPC Megalith Biopharmaceutical Co., Ltd

Overall, both existing literature and our data suggest that RET-FISH testing can be used for rapid screening of RET rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm RET-FISH-positive cases is essential for ensuring that only patients likely to benefit from RET-target therapy receive the treatment.

The prognosis of papillary thyroid carcinoma (PTC) is highly dependent on gene mutations and pathologic features.The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations.These mutations have been suggested to be associated with an increased risk of recurrence,poorer efficacy of postoperative radioactive iodine therapy,and reduced survival.The pathologic subtypes of PTC include classic,follicular,tall cell,hobnail,columnar cell,diffuse sclerosing,solid/trabecular,oncocytic,Warthin-like,clear cell,and spindle cell subtypes,which have different aggressiveness and linked with varied clinical prognosis.Therefore,detecting the gene mutations and pathologic subtypes of PTC is of great importance for therapeutic regimen selection and prognosis evaluation.Ultrasound imaging with non-invasiveness,convenience,and high resolution has become the primary examination method for the diagnosis and treatment of thyroid cancer.This paper reviews the correlations of gene mutations and pathologic subtypes with the ultrasound features of PTC,aiming to give new insights into the application of ultrasound imaging in predicting gene mutations and pathologic subtypes of PTC before surgery as well as provide new ideas for accurate assessment of preoperative prognosis.

This study encapsulates the research endeavors and treatment advancements of RET rearrangement solid tumors within the Chinese healthcare landscape, specifically highlighting the diverse real-world therapeutic approaches and their effectiveness in managing advanced RET rearrangement NSCLC among Chinese patients. Notably, targeted RET inhibitors like Pralsetinib have emerged as potent therapeutic agents, exhibiting remarkable efficacy and a manageable safety profile in this patient cohort. These findings underscore the potential of Pralsetinib and similar targeted therapies as novel treatment options for individuals with RET fusion-positive NSCLC.

P2, N=88, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

The finding of synchronous mutations is a rare occurrence suggesting for intratumoral heterogeneity (ITH) even in PTC. Patients with multiple mutations have a clinical worse prognosis, generally characterized by an aggressive thyroid cancer, which may influence the surgical treatment, chemotherapy, and BRAF V600E mutation-targeting therapy.

Our results regarding the proportion of samples with actionable mutations demonstrate the value of NGS testing for NSCLC patients in a real-world clinical diagnostic setting.

The patient is alive 24 years after resection with no additional recurrences. Bronchial SP needs to be recognized and distinguished from other benign and malignant salivary gland and pulmonary neoplasms so that patients can receive appropriate treatment and follow-up.

P2, N=56, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

Two multi-kinase inhibitors (MKIs) including Cabozantinib and Vandetanib have been shown to increase progression-free survival (PFS) for patients with metastatic MTC and have been approved as choices of first-line treatment...Recently, new generation TKIs, including Selpercatinib and Pralsetinib, have demonstrated highly selective efficacy against RET and more favorable side effect profiles, and gained approval as second-line treatment options...Besides, new promising therapeutic approaches, such as novel drug combinations and next generation RET inhibitors are under development. Herein, we overview the pathogenesis, molecular genetics and current management approaches of MTC, and focus on the recent advances of RET inhibitors, summarize the current situation and unmet needs of these RET inhibitors in MTC, and provide an overview of novel strategies for optimizing therapeutic effects.

We conclude that FFPE-TLC sequencing enables the detection of tumor-specific SVs caused by chromosomal rearrangements and LINE retrotranspositions in FFPE tissue. Therefore, FFPE-TLC sequencing facilitates the investigation of the biological and clinical impact of SVs using FFPE material from (retrospective) cohorts of cancer patients and has potential clinical applicability to detect SV biomarkers in the routine molecular diagnostics setting.

In this study, an increase in M classification cases was found in the RET rearrangements group. However, genetic mutations were not associated with the clinical stage, and no factors that could be incorporated into the treatment algorithm were identified.

No abstract available