Melanoma accounts for a small proportion of skin cancers diagnosed each year, but it has a high degree of malignancy and rapid progression, resulting in a short survival period for patients. The incidence of melanoma continues to rise, and now melanoma accounts for 1.7% of cancer diagnoses worldwide and is the fifth most common cancer in the United States. With the development of high-throughput sequencing technologies, the understanding of the pathophysiology of melanoma had also been improved. The most common activating mutations in melanoma cells are BRAF , NRAS , and KIT mutations, which disrupt cell signaling pathways related to tumor proliferation. The progress has led to the emergence of molecularly targeted drugs, which extends the survival of patients with advanced melanoma. A large number of clinical trials have been conducted to confirm that targeted therapy for patients with advanced melanoma can improve progression-free survival and overall survival, and for stage III patients after radical tumor resection targeted therapy can reduce the recurrence of melanoma. Patients who were originally stage III or IV inoperable have the opportunity to achieve tumor radical resection after targeted therapy. This article reviewed the clinical trial data and summarized the clinical benefits and limitations of these therapies.
Humans ; United States ; Melanoma/genetics* ; Skin Neoplasms/pathology* ; Mutation ; Proto-Oncogene Proteins B-raf/therapeutic use*

<b>OBJECTIVEb>To evaluate the safety and preliminary efficacy of modified FOLFOXIRI (combination of reducing dosage irinotecan, oxaliplatin and fluorouracil) in first-line treatment for patients with metastatic colorectal cancer.

<b>METHODb>A total of 53 patients with advanced colorectal cancer receiving modified FOLFOXIRI regimen were recruited continuously from January 2010 to January 2014. Safety profile was recorded based on NCI Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Objective response was evaluated by Response Evaluation Criteria in Solid Tumors version1.1 (RECIST 1.1) after administration of at least 4 cycles chemotherapy. Kras and Braf gene sequencing was tested by dideoxy chain-termination method. Relation between efficacy and two genes was examined.

<b>RESULTSb>Among 53 patients, no treatment-related mortality was presented. The rate of grade 3 to 4 adverse event was 32.1% (17/53), including neutropenia 13.2%(7/53), anemia 11.3% (6/53) and fatigue 9.4% (5/53). Overall response rate (ORR) and disease control rate (DCR) were respectively 65.9% (29/44) and 90.0% (40/44). Radical resection rate (R0) was 29.5% (13/44). Efficacy of mFOLFOXIRI regimen plus targeting therapy was assessed in 44 patients. mFOLFOXIRI regimen plus targeting therapy achieved an ORR of 72.7% (8/11), which was higher than the ORR 65.9% (21/33) of triplet regimen alone, but the difference was not statistically significant (P=0.198). Paraffin specimens of 48 colorectal cancer cases were tested. Twenty-one cases were Kras mutant (43.75%), 3 cases were Braf mutant (6.25%). There were no significant differences between two groups (P>0.05).

<b>CONCLUSIONb>Reducing dosage mFOLFOXIRI can be safely used in advanced colorectal cancer and can achieve promising results in terms of short term efficacy.

Antineoplastic Agents ; therapeutic use ; Colorectal Neoplasms ; classification ; drug therapy ; genetics ; pathology ; Humans ; Microsatellite Instability ; Mutation ; Polymorphism, Single Nucleotide ; Precision Medicine ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins B-raf ; genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins ; genetics

Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population.
Carcinoma ; genetics ; radiotherapy ; Carcinoma, Papillary ; Humans ; Iodine Radioisotopes ; therapeutic use ; Mutation ; Prognosis ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics ; radiotherapy

Objective:b> To evaluate the clinical characteristics, treatment response, and outcomes in patients with classical hairy cell leukemia (cHCL) and HCL variant (HCL-V). Methods:b> This is a retrospective case series study. Between January 2011 and December 2021, clinical data of 30 patients newly with diagnosed HCL at Peking Union Medical College Hospital were analyzed. The main outcome measures include clinical characteristics, treatment efficacy and survival. The Kaplan-Meier method was used for survival analysis. Results:b> Twenty-one cases of cHCL and 9 cases of HCL-v were included. The median age at diagnosis was 55.5 (range, 30-86) years, with the ratio of male to female 2.75∶1. The main clinical manifestations included fatigue in 11 cases (36.7%), abdominal distension in 7 cases (23.3%), and infection in 4 cases, while 8 cases were asymptomatic. Splenomegaly was reported in 24 cases (80.0%), including 7 (23.3%) with megalosplenia. The white blood cell count, lymphocyte count, and the proportion of peripheral hairy cells in HCL-v group were significantly higher than those in cHCL group, whereas the development of anemia, thrombocytopenia, and monocytopenia in cHCL group was more remarkable than that in HCL-v group (all P<0.05). The BRAF-V600E gene mutation was detected only in cHCL patients (11/14 vs. 0/9, P<0.001). In terms of immunophenotype, the expression of CD25, CD103, CD123 and CD200 in cHCL group (20/20, 20/20, 4/7, 7/17) were all stronger than those in HCL-v group (3/9, 7/9, 0/4, 2/8). Twenty-two patients were treated, of which 13 cases (12 cases of cHCL and 1 case of HCL-v) with cladribine, and 9 cases (4 cHCL and 5 HCL-v) with interferon. Complete remission rate and overall response rate were comparable between cladribine and interferon treatment groups (both P<0.05). The median follow-up time was 31 (range, 1-125) months, and the median overall survival (OS) of the entire group was 125 months. The 5-year OS rate in HCL-v patients represented a trend of inferior (50.0% vs. 95.0%, P=0.207). Conclusions:b> The clinical features of HCL are unspecific, which includes fatigue, splenomegaly and recurrent infection. The clinical features, immunophenotype, treatment response and prognosis of HCL-v are different from those of cHCL. BRAF-V600E gene mutation is suggested as a key marker for differential diagnosis. Cladribine is recommended as front-line regimen of cHCL patients with satisfactory efficacy and prognosis. Conversely, response and clinical outcome in HCL-v patients still need to be improved.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Leukemia, Hairy Cell/drug therapy* ; Cladribine/therapeutic use* ; Splenomegaly/drug therapy* ; Retrospective Studies ; Proto-Oncogene Proteins B-raf/therapeutic use* ; Prognosis ; Interferons/therapeutic use* ; Antineoplastic Agents/therapeutic use*

Hepatocellular carcinoma (HCC) is a major global health problem, which has a grave morbidity and mortality. Over the past few decades, no effective systemic therapeutic modalities have been established for patients with the unresectable HCC in advanced stage. Sorafenib is a small molecule that blocks cancer cell proliferation by targeting the intracellular signaling pathway at the level of Raf-1 and B-Raf serine-threonine kinases, and exerts an anti-angiogenic effect by targeting the vascular endothelial growth factor receptor-1, 2 and 3, and platelet-derived growth factor receptor-beta tyrosine kinases. Recently, two clinical successful applications, SHARP and Asia-Pacific trial, of multikinase inhibitor sorafenib represent a significant advance in the treatment of advanced HCC patients without a curative chance. However, because the results of clinical trials show diverse responses in a subset of HCC patients, a molecular classification of HCC through the excavation of specific biomarkers related to its biological behavior is necessary for sorting HCC patients to each group with a biological homogeneity, ultimately leading to the most suitable individualization of molecular targeted therapy in HCC.
Antineoplastic Agents/therapeutic use ; Benzenesulfonates/therapeutic use ; Carcinoma, Hepatocellular/pathology/secondary/*therapy ; Humans ; Liver Neoplasms/blood supply/pathology/*therapy ; Neovascularization, Pathologic ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-raf/antagonists & inhibitors/metabolism ; Pyridines/therapeutic use ; Receptors, Platelet-Derived Growth Factor/antagonists & inhibitors/metabolism ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors/metabolism ; Signal Transduction

No abstract available.
Antineoplastic Agents/therapeutic use ; Bone Marrow Cells/pathology ; Cladribine/therapeutic use ; DNA Mutational Analysis ; Female ; Humans ; Immunophenotyping ; Leukemia, Hairy Cell/*diagnosis/drug therapy/*genetics ; Middle Aged ; *Mutation ; Proto-Oncogene Proteins B-raf/*genetics ; Reticulin/metabolism

BACKGROUND: Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment. METHODS: Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature. RESULTS: There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib. CONCLUSIONS At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.
Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mice ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins B-raf/genetics*

V-Raf murine sarcoma viral oncogene homolog B (BRAF) alteration is one of the most essential driver genes of non-small cell lung cancer (NSCLC). BRAF encodes serine/threonine protein kinases, and its mutations typically lead to protein compositional activation, thereby activating the mitogen-activated protein kinase kinase (MEK) signaling pathway. A promising new approach for the treatment of mutated BRAF and/or downstream MEK may provide customized treatment opportunities for BRAF driven NSCLC patients. However, combination therapy is necessary to overcome the difficulties such as short duration of benefit, poor therapeutic effect of non-V600 BRAF mutations and susceptibility to drug resistance. This article reviewed the progress in structural characteristics, related signaling pathways, mutation types of BRAF gene, and the clinical pathological relationship between BRAF mutations and NSCLC, as well as the therapy, in order to provide more evidences for clinical doctors to make treatment decisions.
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Animals ; Mice ; Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Proto-Oncogene Proteins B-raf/genetics* ; Mutation ; Mitogen-Activated Protein Kinase Kinases/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Boronic Acids ; therapeutic use ; Bortezomib ; Cervical Intraepithelial Neoplasia ; pathology ; Female ; Human papillomavirus 16 ; isolation & purification ; Humans ; Ovarian Neoplasms ; drug therapy ; metabolism ; pathology ; Papillomavirus Infections ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins B-raf ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Pyrazines ; therapeutic use ; Trastuzumab ; Tumor Suppressor Protein p53 ; metabolism ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; virology ; ras Proteins ; metabolism