Delivering precision oncology to patients with cancer

Mateo, Joaquín; Steuten, Lotte Maria Gertruda; Aftimos, Philippe; Varga, Andrea; Davies, David Mark; Garralda, Elena; Geißler, Jan; Husereau, Don; Martinez-Lopez, Iciar; Normanno, Nicola; Reis‐Filho, Jorge S.; Stefani, Stephen; Thomas, David M.; Westphalen, C. Benedikt; Voest, Emile E.

doi:10.1038/s41591-022-01717-2

Cited by 209 publications

(136 citation statements)

References 55 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…In the near future, we believe that increased knowledge of immune profiling, transcriptomics, and proteomics will provide new means for the stratification of cancer patients and new biomarkers for treatment response. However, the availability of multiple approved treatments for relatively narrow populations of cancer patients is posing significant challenges for healthcare systems [ 138 ]. In this context, it is essential to implement the precision medicine paradigm in clinical practice by adapting the current infrastructures and reimbursement policies to enable access to these anticancer agents for patients [ 138 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Histology-Agnostic Drugs in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Iannantuono

Torino

Rosenfeld

et al. 2022

IJMS

View full text Add to dashboard Cite

Precision medicine has opened up a new era in the development of anti-cancer agents that is focused on identifying biomarkers predictive of treatment response regardless of tumor histology. Since 2017, the Food and Drug Administration has approved six drugs with histology-agnostic indications: pembrolizumab (both for tumors with the mismatch-repair deficiency (dMMR)/high microsatellite instability (MSI-H) phenotype and for those with the high tumor mutational burden (TMB-H) phenotype), dostarlimab (for dMMR tumors), larotrectinib and entrectinib (for tumors harboring neurotrophic tyrosine receptor kinase (NTRK) fusions), and the combination of dabrafenib plus trametinib (for BRAF V600E-mutated tumors). The genomic alterations targeted by these antineoplastic agents are rare in metastatic castration-resistant prostate cancer (mCRPC). Furthermore, only a small number of mCRPC patients were enrolled in the clinical trials that led to the approval of the above-mentioned drugs. Therefore, we critically reviewed the literature on the efficacy of histology-agnostic drugs in mCRPC patients. Although the available evidence derives from retrospective studies and case reports, our results confirmed the efficacy of pembrolizumab in dMMR/MSI-H mCRPC. In contrast, few data are available for dostarlimab, larotrectinib, entrectinib, and dabrafenib-trametinib in this subset of patients. Large, multi-institutional registries aimed at collecting real-world data are needed to better comprehend the role of tissue-agnostic drugs in mCRPC patients.

show abstract

Section: Discussionmentioning

confidence: 99%

The Role of Histology-Agnostic Drugs in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Iannantuono

Torino

Rosenfeld

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…In molecular oncology tumor targeted therapies are based on biomarker results from patient derived cells and tumor tissue. Such stratified treatments have dramatically improved life expectancy for selected groups of patients ( 44 ). In comparison, progress in personalized psychopharmacology has been modest.…”

Section: Discussionmentioning

confidence: 99%

Genome Guided Personalized Drug Therapy in Attention Deficit Hyperactivity Disorder

Haavik

2022

Front. Psychiatry

View full text Add to dashboard Cite

ADHD is a common behavioral syndrome with a heritability of 70–80%. Genome wide sequencing and association studies indicate that ADHD risk variants are distributed across a wide range of allele frequencies and relative risks. Several common single nucleotide variants (SNPs) have been identified that increase the risk of ADHD with a few percent. Many of the reported risk genes and copy number variants are shared with other neuropsychiatric disorders. Moreover, ADHD often coexists with common or rare somatic diseases, including rare Mendelian neurometabolic diseases that can affect normal brain development and function. Some genetic/metabolic syndromes masquerading as common ADHD may lead to irreversible brain damage if not properly identified and treated during early childhood. As ADHD is such a heterogeneous condition in terms of severity, clinical features and most probably also underlying biology, it is crucial to offer individualized treatments. Recent progress in ADHD genetics is reviewed, prospects of using this information for targeted pharmacotherapy are discussed and critical knowledge gaps are identified. It is suggested that genome guided therapies could be introduced gradually, starting with rare ADHD syndromes with highly penetrant risk genes. Routine diagnostic application of whole exome or whole genome sequencing combined with metabolomic screening, and brain imaging may be needed in cases with suspected neurometabolic disorders. Identification and treatment of ADHD patients with defined neurometabolic aberrations could be a first step toward genome guided personalized treatment of ADHD. Possibly, screening for relevant biomarkers may gradually be implemented to guide treatment choices in larger patient groups.

show abstract

“…The recognition that cellular, genetic, and molecular features of cancer allow for segregation of cancer subgroups with different diagnosis, disease progression, and response to treatment, has facil-itated development of therapeutic strategies tailored towards patients most likely to respond while reducing the risk of life-threatening side effects [1,2]. Advances in next-generation sequencing have brought this down to the single cell level, and for many cancerous conditions we now have a detailed overview of the genetic architecture with identification of highly recurrent genetic lesions, as well as molecular profiles based on gene expression, which segregate with different cancer diagnosis, prognosis, and treatment responses [3].…”

Section: Introductionmentioning

confidence: 99%

Targeting stem cells in myelodysplastic syndromes and acute myeloid leukemia

et al. 2022

View full text Add to dashboard Cite

The genetic architecture of cancer has been delineated through advances in high‐throughput next‐generation sequencing, where the sequential acquisition of recurrent driver mutations initially targeted towards normal cells ultimately leads to malignant transformation. Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies frequently initiated by mutations in the normal hematopoietic stem cell compartment leading to the establishment of leukemic stem cells. Although the genetic characterization of MDS and AML has led to identification of new therapeutic targets and development of new promising therapeutic strategies, disease progression, relapse, and treatment‐related mortality remain a major challenge in MDS and AML. The selective persistence of rare leukemic stem cells following therapy‐induced remission implies unique resistance mechanisms of leukemic stem cells towards conventional therapeutic strategies and that leukemic stem cells represent the cellular origin of relapse. Therefore, targeted surveillance of leukemic stem cells following therapy should, in the future, allow better prediction of relapse and disease progression, but is currently challenged by our restricted ability to distinguish leukemic stem cells from other leukemic cells and residual normal cells. To advance current and new clinical strategies for the treatment of MDS and AML, there is a need to improve our understanding and characterization of MDS and AML stem cells at the cellular, molecular, and genetic levels. Such work has already led to the identification of promising new candidate leukemic stem cell molecular targets that can now be exploited in preclinical and clinical therapeutic strategies, towards more efficient and specific elimination of leukemic stem cells.

show abstract

Delivering precision oncology to patients with cancer

Cited by 209 publications

References 55 publications

The Role of Histology-Agnostic Drugs in the Treatment of Metastatic Castration-Resistant Prostate Cancer

The Role of Histology-Agnostic Drugs in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Genome Guided Personalized Drug Therapy in Attention Deficit Hyperactivity Disorder

Targeting stem cells in myelodysplastic syndromes and acute myeloid leukemia

Contact Info

Product

Resources

About