BRAF wild-type

P1, N=18, Suspended, University of Florida | Recruiting --> Suspended

Genomic deletions are also detected in tumor samples from melanoma and breast cancer patients expressing altBRAFs. Along with the identification of altBRAFs in BRAF wild-type and in MAPKi-naive melanoma samples, our results represent a major shift in our understanding of mechanisms leading to the generation of BRAF transcripts variants associated with resistance in melanoma.

Patients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival. ClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892.

P3, N=520, Active, not recruiting, Taizhou Mabtech Pharmaceutical Co.,Ltd | Trial completion date: Jun 2023 --> Jun 2024

P1, N=26, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Jul 2023 | Trial primary completion date: Dec 2023 --> Jul 2023

P1/2, N=30, Not yet recruiting, Brown University | Trial completion date: Aug 2026 --> Jan 2027 | Trial primary completion date: Aug 2024 --> Jan 2025

P2, N=56, Active, not recruiting, Istari Oncology, Inc. | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Jun 2024

Thus, we investigated the effects of ABT-737 and ABT-263, which target Bcl-2, Bcl-xL and Bcl-w as well as the Bcl-2-selective ABT-199 and the Mcl-1-selective S63845, in a panel of four BRAF-mutated and BRAF-WT melanoma cell lines. These findings demonstrate that melanoma cells can be efficiently targeted by BH3 mimetics, but the right combinations have to be selected. The observed pronounced activation of apoptosis pathways demonstrates the decisive role of apoptosis in the loss of cell viability by BH3 mimetics.

At present, standard of care first-line treatment for those with HER2-positive mCRC remains chemotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors or bevacizumab, depending on RAS/BRAF mutational status and tumor sidedness...While the choice of anti-HER2 therapy is empiric given lack of head-to-head comparisons, the combination of trastuzumab plus tucatinib has received FDA accelerated approval for use in this setting and is generally the authors' preference. Trastuzumab plus lapatinib, trastuzumab plus pertuzumab, and trastuzumab deruxtecan (T-DXd) also have evidence of efficacy in this setting...These include the optimal sequence of anti-HER2 therapies with chemotherapy and anti-EGFR therapies, the optimal combination partners for anti-HER2 therapies, and the incorporation of predictive biomarkers to guide use of anti-HER2 therapies. Results of ongoing studies may thus alter the treatment paradigm above in the coming years.

Therefore, clinical relevance exists for analyses of MSI and MSI-H-associated genomic alterations in malignancy. In this article, we provide an update on MSI-driven carcinogenesis, with an emphasis on unique landscapes of diagnostic and immunotherapeutic strategies.

P2, N=34, Recruiting, National Cancer Institute, Naples | Trial completion date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2024 --> May 2023

P1, N=27, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

P1/2, N=24, Recruiting, Sun Yat-sen University | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=198, Recruiting, Sun Yat-sen University | Active, not recruiting --> Recruiting

Resistant gene mutations caused by anti-EGFR drugs in RAS/BRAF wild-type mCRC patients can be observed by dynamic ctDNA analysis. TP53 and AMER1 mutations, tumor mutational burden (TMB) levels, and TP53/AMER1 co-mutation may predict the efficacy of the first-line cetuximab-contained treatment. Situations of genetic mutations were differentiated from first-line PD to second-line PD, which indicated that mutation detection may contribute to predict prognosis of mCRC patients.

Plasma-based liquid biopsy does not seem to be an accurate method for the detection of the BRAF V600E mutation in circulating circulating cell-free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.

At a median follow up of 96.2 months, the median OS for codon 61 RAS-mutated patients was significantly shorter compared to RAS/BRAF wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 RAS-mutated and BRAF V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary.

The results of this study confirm a clinically significant benefit of trastuzumab plus pertuzumab treatment in patients with HER2+mCRC.

P2, N=176, Active, not recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Nov 2024

Encouraged by its efficacy, it was further investigated for its antitumor activity and mechanism of action, using sorafenib as a reference standard...It also downregulated Notch1 protein expression and decreased TGF-β1 production. Molecular docking simulations suggest that 8e binds as a promising type II kinase inhibitor in the target kinases interacting with the key regions in their kinase domain.

Moreover, multigene detection is superior to single gene detection. For BSRTC Ⅲ lesion with wild-type BRAF, multigene detection can be considered with a repeated FNA.

Conclusion Transfer learning and self-supervised cross-training improved classification performance and generalizability for noninvasive pLGG mutational status prediction in a limited data scenario.

They were randomly assigned to the control group of FLOX (oxaliplatin, 5-fluorouracil, folinic acid) Q2W or the experimental group of alternating 2 cycles each of FLOX Q2W and nivolumab Q2W, with prespecified break periods. TMB >5 mut/Mb was associated with tumor KRAS or BRAF driver mutation and remarkably long PFS in first-line treatment of patients with abdominal metastases from MSS-CRC with alternating short-course oxaliplatin-based chemotherapy and ICB.

P2, N=74, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting | N=362 --> 74

P3, N=674, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Apr 2024 --> Nov 2024

P1, N=20, Active, not recruiting, Lawson Health Research Institute | Trial completion date: Dec 2023 --> Dec 2024

The pivotal trials of cetuximab in combination with BRAF/ MEK inhibitor for BRAF V600E mutant mCRC, and panitumumab with KRAS G12C inhibitor in KRAS(G12C)-mutant mCRC have been practice-changing. The non-invasive monitoring of molecular resistance to targeted therapies using Next Generation Sequencing analysis of circulating tumor-derived DNA (ctDNA) and captured sequencing of tumors have improved patient selection for targeted therapies. This review will focus on how latest advances, challenges and future directions in the development of targeted therapies in mCRC.

The simultaneous occurrence of adrenal and thyroid autoimmune diseases, resembling autoimmune polyendocrine syndrome type 2, may occur as a rare but serious side effect of ICI treatment. It often presents with abrupt onset and rapid evolution towards polyglandular insufficiency. Physicians should be aware of the potential association of two or more endocrine disorders and careful monitoring of endocrine function is needed during ICI therapy.

Patients with RAS/BRAFV600E wt mCRC according to tissue genotyping who benefited from previous anti-EGFR-based treatment (fluoropyrimidines, oxaliplatin, irinotecan, and antiangiogenics) and then experienced disease progression to EGFR targeting were eligible for screening in the PARERE trial. This is the largest prospective cohort of mCRC patients screened with LB for anti-EGFR retreatment in a randomized study. ctDNA genotyping reveals that at least one out of three patients candidate for retreatment should be excluded from this therapy, and other potential drivers of anti-EGFR resistance are found in approximately one out of three patients with RAS/BRAFV600E wt ctDNA.

P1/2, N=33, Recruiting, University of Utah | Not yet recruiting --> Recruiting

P=N/A, N=51, Recruiting, Shanghai Minimally Invasive Surgery Center | Trial primary completion date: Jun 2023 --> Aug 2024

No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + TCM cell expansion associated with favorable pathologic responses (exploratory outcome).

The diagnosis of SWI/SNF-deficient undifferentiated carcinoma can be challenging. Correlation with clinical findings, in conjunction with IHC work-up and molecular analysis, is of utmost importance to arrive at the appropriate diagnosis and exclude potential mimics.

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025

P1/2, N=217, Completed, Amgen | Phase classification: P1b/2 --> P1/2

CNPTC is sensitive but not specific for BRAF mutational status. SSN, PPC, and CNPTC are not predictive markers for the presence of BRAF mutation or histologic subtypes. Additional studies may be needed to further corroborate these findings.

This study showed class 1/non-class 1 BRAF mutation in CRC had significantly differences in co-mutation features, genomic markers and prognostic. Understanding BRAF mutation types and comutation mechanism will contribute to accurately grasping treatment and follow-up strategies and promoting the development of precision therapy for CRC in the future.

The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.

In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings.

P1/2, N=130, Recruiting, Anaveon AG | Trial primary completion date: Jun 2024 --> Sep 2024

P2, N=24, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Jan 2026 --> May 2023

P1, N=39, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024