Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns

Mateo, Lídia; Duran‐Frigola, Miquel; Gris-Oliver, Albert; Palafox, Marta; Scaltriti, Maurizio; Razavi, Pedram; Chandarlapaty, Sarat; Arribas, Joaquı́n; Bellet, Meritxell; Serra, Violeta; Aloy, Patrick

doi:10.1186/s13073-020-00774-x

Cited by 17 publications

(9 citation statements)

References 87 publications

(170 reference statements)

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“…Yet, recent data have suggested the potential for rational combinations in targeted therapy to improve outcomes, along with the value of considering co-occurring alterations to improve the prediction of benefit. 39,40 We envision that the number of basket trials will continue to expand in the coming years, with a growing number of trials evaluating novel targets, rational combinations, and antibody-drug conjugates, along with presenting enhanced entry criteria on the basis of consideration of co-occurring mutations.…”

Section: Context Key Objectivementioning

confidence: 99%

Basket Trials: Review of Current Practice and Innovations for Future Trials

Hobbs

Pestana

Zabor

et al. 2022

JCO

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Advances in biology and immunology have elucidated genetic and immunologic origins of cancer. Innovations in sequencing technologies revealed that distinct cancer histologies shared common genetic and immune phenotypic traits. Pharmacologic developments made it possible to target these alterations, yielding novel classes of targeted agents whose therapeutic potential span multiple tumor types. Basket trials, one type of master protocol, emerged as a tool for evaluating biomarker-targeted therapies among multiple tumor histologies. Conventionally conducted within the phase II setting and designed to estimate high and durable objective responses, basket trials pose challenges to statistical design and interpretation of results. This article reviews basket trials implemented in oncology studies and discusses issues related to their statistical design and analysis.

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Section: Context Key Objectivementioning

confidence: 99%

Basket Trials: Review of Current Practice and Innovations for Future Trials

Hobbs

Pestana

Zabor

et al. 2022

JCO

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“…Half (N = 22) of the defective genes listed here are identified by the Cancer Genome Interpreter's encyclopedia of patient-derived tumor xenografts (PDX) as driver mutations. A recent report using driver mutation patterns for prioritization of personalized cancer therapy [132] finds nearly 20% of their 39 tumor biomarkers to be included in this set of defective genes. Although the defective genes listed here were derived from novel applications of bioinformatic tools, these results find support within other databases.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action

Covell

2021

PLoS ONE

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A joint analysis of the NCI60 small molecule screening data, their genetically defective genes, and mechanisms of action (MOA) of FDA approved cancer drugs screened in the NCI60 is proposed for identifying links between chemosensitivity, genomic defects and MOA. Self-Organizing-Maps (SOMs) are used to organize the chemosensitivity data. Student’s t-tests are used to identify SOM clusters with enhanced chemosensitivity for tumor cell lines with versus without genetically defective genes. Fisher’s exact and chi-square tests are used to reveal instances where defective gene to chemosensitivity associations have enriched MOAs. The results of this analysis find a relatively small set of defective genes, inclusive of ABL1, AXL, BRAF, CDC25A, CDKN2A, IGF1R, KRAS, MECOM, MMP1, MYC, NOTCH1, NRAS, PIK3CG, PTK2, RPTOR, SPTBN1, STAT2, TNKS and ZHX2, as possible candidates for roles in chemosensitivity for compound MOAs that target primarily, but not exclusively, kinases, nucleic acid synthesis, protein synthesis, apoptosis and tubulin. These results find exploitable instances of enhanced chemosensitivity of compound MOA’s for selected defective genes. Collectively these findings will advance the interpretation of pre-clinical screening data as well as contribute towards the goals of cancer drug discovery, development decision making, and explanation of drug mechanisms.

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“…It uses genetics as well as environmental biomarkers to determine diagnoses, prognosis therapeutic options for patients, and accurate dosing. Precision medicine classifies diseases using genome sequencing to identify patients who have tumors exhibiting actionable targets and promoting more informed and accurate treatment decisions [ 81 ]. Mutations in prostate cancer-related genes BRCA1 and BRCA2 render men with mCRPC suitable for treatment with either rucaparib or olaparib, and other prostate cancer genes that have responded well to olaparib treatment, which include ATM , CDK12 , CHECK2 , CHECK1 , PALB2 , PP2R2A, and RAD54L [ 82 ].…”

Section: Methodsmentioning

confidence: 99%

Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches

et al. 2022

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Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate cancer present with either a localized or advanced disease. In this review, we aim to provide a holistic overview of prostate cancer, including the diagnosis of the disease, mutations leading to the onset and progression of the disease, and treatment options. Prostate cancer diagnoses include a digital rectal examination, prostate-specific antigen analysis, and prostate biopsies. Mutations in certain genes are linked to the onset, progression, and metastasis of the cancer. Treatment for localized prostate cancer encompasses active surveillance, ablative radiotherapy, and radical prostatectomy. Men who relapse or present metastatic prostate cancer receive androgen deprivation therapy (ADT), salvage radiotherapy, and chemotherapy. Currently, available treatment options are more effective when used as combination therapy; however, despite available treatment options, prostate cancer remains to be incurable. There has been ongoing research on finding and identifying other treatment approaches such as the use of traditional medicine, the application of nanotechnologies, and gene therapy to combat prostate cancer, drug resistance, as well as to reduce the adverse effects that come with current treatment options. In this article, we summarize the genes involved in prostate cancer, available treatment options, and current research on alternative treatment options.

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Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns

Cited by 17 publications

References 87 publications

Basket Trials: Review of Current Practice and Innovations for Future Trials

Basket Trials: Review of Current Practice and Innovations for Future Trials

Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action

Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches

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