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Genomics/Genetics
Survivorship

Germline Cancer-Predisposing Variants and Increased Risk of Late Mortality From Subsequent Malignant Neoplasms in Long-Term Childhood Cancer Survivors

In an analysis from the St. Jude Lifetime Cohort (SJLIFE) and Childhood Cancer Survivor Study (CCSS) reported in The Lancet Oncology, Chen et al found that among long-term survivors of childhood cancers, carriers of germline cancer-predisposing variants were at an increased risk of late mortality...

Solid Tumors
Genomics/Genetics

FDA Expands Pediatric Indication for Entrectinib and Approves New Pellet Formulation

On October 20, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the small-molecule tyrosine kinase inhibitor entrectinib (Rozlytrek) for pediatric patients aged 1 month and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion...

Solid Tumors
Genomics/Genetics

Almost Half of Oncology Drugs Approved Since 1998 Have Been Precision Therapies, New Study Finds

Among the 198 new oncology drugs approved by the U.S. Food and Drug Administration (FDA) between 1998 and 2022, approximately 43% of them were precision therapies, according to a recent study published by Suehnholz et al in Cancer Discovery. Background Precision oncology therapies often require...

Issues in Oncology
Genomics/Genetics

The Future of AI in Cancer Care

New research has illustrated the strides being made to apply modern artificial intelligence (AI) computing methods to oncology, according to new findings to be presented at the European Society for Medical Oncology (ESMO) Congress 2023. Background Researchers have long investigated the potential of ...

Breast Cancer
Genomics/Genetics

Prophylactic Salpingo-Oophorectomy and Survival After Resection of Germline BRCA1/2-Mutant Breast Cancer

In an Italian single-institution retrospective study reported in JAMA Surgery, Martelli et al found that prophylactic salpingo-oophorectomy was associated with improved overall survival in patients who had undergone resection of germline BRCA1/2-mutant breast cancer. Study Details The study...

Prostate Cancer
Genomics/Genetics

Germline Variants and Risk of Aggressive Prostate Cancer

In a study reported in JAMA Oncology, Darst et al identified germline genetic variants that were associated with increased risk of aggressive vs nonaggressive prostate cancer. As stated by the investigators, “Germline gene panel testing is recommended for men with advanced prostate cancer or a...

Lung Cancer
Immunotherapy
Genomics/Genetics

Expert Point of View: Justin F. Gainor, MD

Justin F. Gainor, MD, Director of the Center for Thoracic Cancers Program at Massachusetts General Hospital, Boston, was invited to discuss IMpower151 and ILLUMINATE at the 2023 World Conference on Lung Cancer. IMpower151 vs IMpower150 Dr. Gainor examined why IMpower151 was negative for both...

Immunotherapy
Lung Cancer
Genomics/Genetics

Checkpoint Inhibitors Offer Limited Benefit in EGFR-Mutated Lung Cancer After Disease Progression

In advanced non–small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR), the role of immune checkpoint inhibitors following disease progression with tyrosine kinase inhibitors has been unclear. Several studies reported at the International Association for the Study ...

Lung Cancer
Genomics/Genetics

Expert Point of View: Roy S. Herbst, MD, PhD

Roy S. Herbst, MD, PhD, cautioned that although FLAURA2 is a positive result, most patients will still develop drug resistance. “The result is really good and clearly positive, but if you look at the survival curves, there is still early overlap in a way that makes it unlikely this combination will ...

Lung Cancer
Genomics/Genetics

FLAURA2 Trial: Osimertinib Plus Chemotherapy Improves Outcomes in Advanced EGFR-Positive NSCLC

First-line treatment with osimertinib plus platinum-based chemotherapy achieved a statistically significant and clinically meaningful progression-free survival improvement compared with osimertinib alone in patients with advanced epidermal growth factor receptor (EGFR)-mutated non–small cell lung...

lung cancer
genomics/genetics

Xiuning Le, MD, PhD, on Update on the Use of Tepotinib to Treat an NSCLC Subset

Xiuning Le, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses results of the VISION trial, the largest on-treatment liquid biopsy biomarker data set of a MET inhibitor in patients with MET exon 14 non–small cell lung cancer (NSCLC). Tepotinib showed durable efficacy in this population.

lung cancer
genomics/genetics

Seshiru Nakazawa, MD, PhD, on NSCLC and Point Mutations as de Novo Oncogenic Drivers

Seshiru Nakazawa, MD, PhD, of Dana-Farber Cancer Institute, discusses activating the MET tyrosine kinase domain mutation, which has been identified as the sole oncogenic mutation in a small but significant subset of patients with non–small cell lung cancer (NSCLC). According to Dr. Nakazawa’s findings, this mutation is potentially targetable with currently available MET tyrosine kinase inhibitors.

Genomics/Genetics

FDA Grants First Marketing Authorization for a DNA Test to Assess Predisposition for Dozens of Cancer Types

On September 29, the U.S. Food and Drug Administration (FDA) granted de novo marketing authorization for the Invitae Common Hereditary Cancers Panel, an in vitro diagnostic test that may help detect hundreds of genetic variants associated with an elevated risk of developing certain cancers. The...

genomics/genetics

Desheng Liang, MD, PhD, on Genetic Engineering of Mesenchymal Stem Cells for Cancer Therapy

Desheng Liang, MD, PhD, of China’s Central South University, discusses the ability of mesenchymal stem cells to target tumor and the progress he and his team have made in genetically engineering these cells for cancer treatment. Mesenchymal cells, which hold promise for therapeutic advances, are safe and relatively simple to produce, according to Dr. Liang.

CNS Cancers
Genomics/Genetics

First-Line Dabrafenib/Trametinib in Pediatric BRAF V600–Mutated Low-Grade Glioma

In a phase II trial reported in The New England Journal of Medicine, Eric Bouffet, MD, and colleagues found that the combination of dabrafenib and trametinib produced a higher objective response rate vs standard chemotherapy in the first-line treatment of pediatric patients with low-grade glioma...

Prostate Cancer
Genomics/Genetics

Mutations in 11 Genes May Be Associated With Aggressive Prostate Cancer

Researchers have singled out mutations in 11 genes associated with aggressive types of prostate cancer, according to a novel study published by Darst et al in JAMA Oncology. The new findings may lead to improvements in diagnosis and treatment. Background Currently, oncologists use genetic tests to...

Lung Cancer
Genomics/Genetics
Immunotherapy

Do Checkpoint Inhibitors Show Benefit in EGFR-Mutated NSCLC After Progression?

In patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR mutations, the role of immune checkpoint inhibitors following disease progression with tyrosine kinase inhibitors has been unclear. Several studies reported at the International Association for the Study of Lung Cancer 2023 ...

Head and Neck Cancer
Genomics/Genetics

Personalized Biomarker-Based Umbrella Trial in Recurrent or Metastatic HNSCC

In a Korean phase II trial (KCSG HN 15-16 TRIUMPH) reported in the Journal of Clinical Oncology, Keam et al described results of a personalized biomarker-driven umbrella trial for the treatment of patients with platinum-refractory recurrent and/or metastatic head and neck squamous cell carcinoma...

Issues in Oncology
Genomics/Genetics

Patients With Cancer and DPYD Variant Alleles: Outcomes With Reduced-Dose Fluoropyrimidine Therapy

In an analysis reported in the Journal of Clinical Oncology, Knikman et al found that reduced doses of fluoropyrimidine therapy in patients with cancer with DPYD variant alleles did not result in poorer outcomes vs DPYD wild-type controls receiving full fluoropyrimidine doses. Study Details The...

genomics/genetics

Aaron C. Tan, PhD, MBBS, on Circulating Tumor DNA: Early Biomarker of Therapeutic Response in Phase I Trials

Aaron C. Tan, PhD, MBBS, of the National Cancer Centre Singapore, discusses new findings on early evaluation of circulating tumor DNA via low-pass whole-genome sequencing. The results of his study suggest this method may represent an early pharmacodynamic biomarker of therapeutic response (particularly for targeted treatments) that may influence decisions on dose determination (Abstract 23).

Pancreatic Cancer
Genomics/Genetics

Germline Predisposition and Homologous Recombination Deficiency in Pancreatic Acinar Cell Carcinoma

In a study reported in the Journal of Clinical Oncology, Mandelker et al found that pancreatic acinar cell carcinoma was associated with a high prevalence of BRCA2 germline pathogenic variants and genomic features of homologous recombination deficiency (HRD). The study involved somatic and germline ...

Myelodysplastic Syndromes
Genomics/Genetics

Allogeneic HCT Outcomes in Patients With MDS and High-Risk Genetics

In a genetic analysis from the Blood and Marrow Transplant Clinical Trials Network 1102 Study reported in the Journal of Clinical Oncology, Versluis et al found that allogeneic hematopoietic cell transplantation (HCT) improved overall survival compared with non-HCT treatment in patients with...

Genomics/Genetics

23andMe Granted FDA 510(k) Clearance to Report Additional BRCA Variants

23andMe has announced that the company has received a U.S. Food and Drug Administration (FDA) 510(k) clearance to expand its existing BRCA1/BRCA2 (Selected Variants) Genetic Health Risk Report. The clearance allows 23andMe to report an additional 41 variants in the BRCA1 and BRCA2 genes known to be ...

Solid Tumors
Genomics/Genetics

Divarasib in Patients With Advanced Solid Tumors and a KRAS G12C Mutation

In a phase I study reported in The New England Journal of Medicine, Sacher et al found that the covalent KRAS G12C inhibitor divarasib (also referred to as GDC-6036) produced durable responses in patients with advanced or metastatic solid tumors with a KRAS G12C mutation. In the study, 137 patients ...

Leukemia
Genomics/Genetics

Understanding How TET2 Gene Deficiency May Fuel Development of AML

Researchers may have identified how the TET2 gene may fuel rapid cancer growth in patients with acute myeloid leukemia (AML), according to a recent study published by Li et al in Cell Stem Cell. Background AML is distinguished by the rapid division and metastasis of immature leukemia stem cells....

Breast Cancer
Genomics/Genetics

Researchers May Have Identified Several New Breast Cancer Susceptibility Genes

Researchers have identified genes that may be associated with breast cancer and could eventually be included in tests to identify high-risk patients, according to a recent study published by Wilcox et al in Nature Genetics. Background Currently, genetic tests for breast cancer consider a few genes...

Breast Cancer
Gynecologic Cancers
Genomics/Genetics

Therapeutic Implications of DNA Repair Discoveries in Patients With Homologous Recombination Deficiencies

Long-molecule scars may help identify patients with BRCA1- and BRCA2-deficient cancer types, according to a recent study published by Setton et al in Nature. Background Once DNA is damaged by toxins, radiation, or normal cell division, human cells must continually fix DNA breaks to survive. When...

Bladder Cancer
Genomics/Genetics

Diagnosing Early-Stage Bladder Cancer in Patients With Hematuria: Novel mePENK Test

Researchers have found that the new PENK methylation (mePENK) test could potentially pave the way for a breakthrough in early bladder cancer detection in patients with hematuria, according to a novel study published by Oh et al in The Journal of Molecular Diagnostics. The findings could reduce the...

Bladder Cancer
Genomics/Genetics

Expert Point of View: Daniel P. Petrylak, MD

“Clinically, the implications [of the THOR trial] are clear in that all metastatic urothelial cancers should be tested for FGFR mutations,” stated invited discussant Daniel P. Petrylak, MD, of Yale School of Medicine. “This should be done at the beginning of treatment for metastatic disease, as it...

Bladder Cancer
Genomics/Genetics

THOR Trial: Erdafitinib Improves Outcomes vs Chemotherapy in FGFR-Altered Advanced Urothelial Carcinoma

Targeted treatment with the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib significantly improved overall survival, progression-free survival, and objective response rates compared with investigator’s choice of chemotherapy in patients with advanced urothelial cancers and FGFR2/3...

Prostate Cancer
Genomics/Genetics

Rucaparib vs Physician’s Choice of Single-Agent Therapy in BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer

As reported in The New England Journal of Medicine by Karim Fizazi, MD, PhD, of Gustave Roussy Institute, Paris-Saclay University, and colleagues, the phase III TRITON3 trial has shown significantly improved progression-free survival with rucaparib vs physician-selected single-agent therapy in the...

Prostate Cancer
Genomics/Genetics

FDA Approves Niraparib and Abiraterone Acetate Plus Prednisone for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer

On August 11, the U.S. Food and Drug Administration (FDA) approved the fixed-dose combination of niraparib and abiraterone acetate (Akeega), with prednisone, for adult patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer, as determined by...

Lung Cancer
Genomics/Genetics

FDA Approves Pralsetinib for RET Fusion–Positive NSCLC

On August 9, the U.S. Food and Drug Administration (FDA) granted regular approval to pralsetinib (Gavreto) for adults with metastatic RET fusion–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test. ARROW Trial Pralsetinib was previously granted accelerated approval for...

Solid Tumors
Genomics/Genetics

Erdafitinib for Patients With FGFR-Altered Advanced Solid Tumors

In the phase II RAGNAR study reported in The Lancet Oncology, Shubham Pant, MBBS, and colleagues found that the pan-FGFR tyrosine kinase inhibitor erdafitinib showed activity in patients with advanced solid tumors with FGFR alterations. Study Details In the ongoing study, 217 patients aged ≥ 12...

Leukemia
Genomics/Genetics

Outcomes in Pediatric ALL With Prolonged Therapy for IKZF1 Deletion and Reduced Therapy for Other Risk Groups

In a recent study (Dutch Childhood Oncology Group [DCOG] ALL11) reported in the Journal of Clinical Oncology, Pieters et al found that modifications in therapy appeared to improve outcomes and reduce drug exposure in pediatric patients with acute lymphoblastic leukemia (ALL) compared with treatment ...

Skin Cancer
Genomics/Genetics

Atezolizumab, Vemurafenib, and Cobimetinib in Patients With BRAF V600–Mutated Melanoma and CNS Metastases

A revised report of findings from the phase II TRICOTEL study of atezolizumab, vemurafenib, and cobimetinib in patients with melanoma and central nervous system (CNS) metastases was published in The Lancet Oncology by Reinhard Dummer, MD, and colleagues. The first version of trial findings,...

Bladder Cancer
Genomics/Genetics

Expert Point of View: Daniel P. Petrylak, MD

“Clinically, the implications [of the THOR trial] are clear in that all metastatic urothelial cancers should be tested for FGFR mutations,” stated invited discussant Daniel P. Petrylak, MD, of Yale School of Medicine. “This should be done at the beginning of treatment for metastatic disease, as it...

Bladder Cancer
Genomics/Genetics

THOR Trial: Erdafitinib Improves Outcomes vs Chemotherapy in FGFR-Altered Advanced Urothelial Carcinoma

Targeted treatment with the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib significantly improved overall survival, progression-free survival, and objective response rates compared with investigator’s choice of chemotherapy in patients with advanced urothelial cancers and FGFR2/3...

Leukemia
Genomics/Genetics

FDA Approves Quizartinib for Newly Diagnosed FLT3-ITD–Positive Acute Myeloid Leukemia

On July 20, the U.S. Food and Drug Administration (FDA) approved quizartinib (Vanflyta) with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adults with newly diagnosed acute...

Lung Cancer
Genomics/Genetics

Adjuvant Osimertinib in Resected EGFR-Mutant NSCLC: Overall Survival Analysis of the ADAURA Trial

As reported in The New England Journal of Medicine by Masahiro Tsuboi, MD, and colleagues, the planned final overall survival analysis of the phase III ADAURA trial has shown a significant benefit with osimertinib vs placebo in patients with resected EGFR-mutant non–small cell lung cancer (NSCLC)....

Lung Cancer
Genomics/Genetics

Lazertinib vs Gefitinib in the First-Line Treatment of EGFR-Mutated Advanced NSCLC

In a phase III trial (LASER301) reported in the Journal of Clinical Oncology, Byoung Chul Cho, MD, PhD, and colleagues found that lazertinib improved progression-free survival vs gefitinib in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC). As stated by the...

Lung Cancer
Genomics/Genetics

APOBEC3A Protein May Be Linked to Drug Resistance in Patients With NSCLC

Researchers have uncovered how non–small cell lung cancer (NSCLC) tumors may develop drug resistance over time and identified the APOBEC3A protein as a potential target for novel cancer therapeutics, according to a study published by Isozaki et al in Nature. The findings point to potential...

Lung Cancer
Genomics/Genetics

Use of Zipalertinib in Previously Treated Patients With Advanced NSCLC and EGFR Exon 20 Insertions

In a phase I/IIa study reported in the Journal of Clinical Oncology, Piotrowska et al found that the EGFR tyrosine kinase inhibitor zipalertinib showed activity and an acceptable safety profile in previously treated patients with advanced non–small cell lung cancer (NSCLC) and EGFR exon 20...

Lung Cancer
Genomics/Genetics

Pembrolizumab-Based Combination Therapies May Improve Outcomes in Advanced NSCLC

Researchers have revealed that combining pembrolizumab with other treatments may reduce the size of target tumors, resulting in a higher response rate for patients with advanced non–small cell lung cancer (NSCLC), according to a recent study published by Gutierrez et al in Nature Medicine. “We are...

Colorectal Cancer
Genomics/Genetics

Germline Variants in Colorectal Cancer Susceptibility Genes by Race/Ethnicity in Patients With Early-Onset Colorectal Cancer

In a study reported in the Journal of Clinical Oncology, Seagle et al identified the prevalence of germline colorectal cancer susceptibility gene variants according to race and ethnicity among patients with early-onset colorectal cancer. Study Details The study involved patients aged 15 to 49 years ...

Hepatobiliary Cancer
Genomics/Genetics

EGFR and ERBB2 Mutations May Be Associated With Lenvatinib-Resistant Hepatocellular Carcinoma

A genetic marker involving the EGFR and ERBB2 genes may be predictive of which patients with hepatocellular carcinoma are most likely to develop resistance to lenvatinib, according to a study published by Lim et al in Gastroenterology. The new findings could help researchers develop alternative...

Colorectal Cancer
Genomics/Genetics

Expert Point of View: Lisa Newman, MD, MPH, FACS, FASCO

Commenting on this study on clinical genomic profiling for colorectal cancer, Lisa Newman, MD, MPH, FACS, FASCO, Chief of the Section of Breast Surgery and leader of the Multidisciplinary Breast Oncology Programs at Weill Cornell Medicine and NewYork-Presbyterian, commended the authors for...

Colorectal Cancer
Genomics/Genetics

Retrospective Study Finds Black Patients With Colorectal Cancer Had Fewer Actionable Genomic Mutations Than White Patients

Black individuals have a higher incidence of colorectal cancer than White individuals, and their outcomes are worse. Undoubtedly, reasons for this are multifaceted, but the disparity in outcomes may be partly explained by genomic differences, documented in a large retrospective study presented at...

Colorectal Cancer
Genomics/Genetics

Effect of Upregulated KDM5D Gene on Y Chromosome in Male Patients With KRAS-Mutated Colorectal Cancer

Researchers have revealed that the KDM5D gene on the Y chromosome, which is upregulated in KRAS-mutated colorectal cancer, may be responsible for increasing tumor cell invasiveness and reducing antitumor immunity in male patients, according to a recent study published by Li et al in Nature. The new ...

Bladder Cancer
Genomics/Genetics

Loss of Y Chromosome in Men and Bladder Cancer Progression

Researchers have found that the loss of the Y chromosome, a common impact of the aging process in men, may help cancer cells evade the body’s immune system and result in aggressive bladder cancer—but it may also render the disease more vulnerable and responsive to immune checkpoint...

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