Missing the target in cancer therapy

Adashek, Jacob J.; Goloubev, Alexey; Kato, Shumei; Kurzrock, Razelle

doi:10.1038/s43018-021-00204-w

Cited by 28 publications

(27 citation statements)

References 16 publications

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“…There have been limited successes with the use of targeted therapy in pancreatic cancer, perhaps because only a minority of pancreatic cancer trials use a biomarker for enrolling patients 26 . It is clear that a biomarker-driven approach has driven advances for other cancers.…”

Section: Discussionmentioning

confidence: 99%

Personalized matched targeted therapy in advanced pancreatic cancer: a pilot cohort analysis

Shaya¹,

Kato²,

Adashek³

et al. 2023

npj Genom. Med.

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Despite progress, 2-year pancreatic cancer survival remains dismal. We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board). Targeted agents administered/patient = 2.5 (median) (range, 1–4); first-line therapy (N = 5); second line, (N = 13). Comparing patients (high versus low degrees of matching) (matching score ≥50% versus <50%; reflecting number of alterations matched to targeted agents divided by number of pathogenic alterations), survival was significantly longer (hazard ratio [HR] 0.24 (95% confidence interval [CI], 0.078–0.76, P = 0.016); clinical benefit rates (CBR) (stable disease ≥6 months/partial/complete response) trended higher (45.5 vs 0.0%, P = 0.10); progression-free survival, HR, 95% CI, 0.36 (0.12–1.10) (p = 0.075). First versus ≥2nd-line therapy had higher CBRs (80.0 vs 7.7%, P = 0.008). No grade 3–4 toxicities occurred. The longest responder achieved partial remission (17.5 months) by co-targeting MEK and CDK4/6 alterations (chemotherapy-free). Therefore, genomically matched targeted agent combinations were active in these advanced pancreatic cancers. Larger prospective trials are warranted.

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Section: Discussionmentioning

confidence: 99%

Personalized matched targeted therapy in advanced pancreatic cancer: a pilot cohort analysis

Shaya¹,

Kato²,

Adashek³

et al. 2023

npj Genom. Med.

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“…Within these all-comer trials using targeted agents, a signal might be lost in the noise of non-responses. [79] More recently, these issues have been addressed in biomarker-based trials for gene-targeted agents. However, these trials are mostly geared towards a single targeted agent and its cognate molecular anomaly.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

“…For immunotherapy, clinical trials are still typically applied to populations without a biomarker, and without immunomic analysis. [79] Taking the concept of tumor heterogeneity into account and aiming to overcome this phenomenon is key. [80] Heterogeneity can occur between patients or within a patient.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Cancer: slaying the nine-headed Hydra

Adashek¹,

Subbiah²,

Westphalen³

et al. 2023

Annals of Oncology

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“…Precision medicine utilizes specific molecular biomarkers to assess a single individual’s condition or neoplasm, so that a precise—and, optimally, most effective—treatment for that person with disease-directed drugs or tumor-targeted agents can be determined [ 1 – 3 ]. Disease-directed antibiotic therapy is used to manage patients with infectious conditions [ 4 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions—Precision Dermatology

Cohen

Kurzrock

2022

Dermatol Ther (Heidelb)

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Precision dermatology uses individualized dermatologic disease-directed targeted therapy (D 3 T 2 ) for the management of dermatoses and for the evaluation and therapy of cutaneous malignancies. Personalized/precision strategies are based on biomarkers that are most frequently derived from tissue transcriptomic expression or genomic sequencing or from circulating cytokines. For instance, the pathologic diagnosis of a pigmented lesion and determining the prognosis of a malignant melanocytic neoplasm can be enhanced by genomic/transcriptomic analysis. In addition to biopsy, innovative techniques have been developed for

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Missing the target in cancer therapy

Cited by 28 publications

References 16 publications

Personalized matched targeted therapy in advanced pancreatic cancer: a pilot cohort analysis

Personalized matched targeted therapy in advanced pancreatic cancer: a pilot cohort analysis

Cancer: slaying the nine-headed Hydra

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions—Precision Dermatology

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