Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications

Gouda, Mohamed A.; Nelson, Blessie Elizabeth; Buschhorn, Lars; Wahida, Adam; Subbiah, Vivek

doi:10.1158/1078-0432.ccr-23-0090

Cited by 28 publications

(12 citation statements)

References 86 publications

(36 reference statements)

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“…This holistic approach recognizes that each patient’s response to treatment may vary based on factors beyond their tumor’s genetic makeup. Therefore, precision medicine involves a comprehensive evaluation of both the tumor and the patient, allowing oncologists to make more informed decisions about the most suitable therapy …”

Section: Overview Of Colorectal Cancer and Precision Medicinementioning

confidence: 99%

“…Targeted therapies and immunotherapies, two key components of precision medicine, aim to attack cancer cells specifically while sparing healthy tissues. For example, monoclonal antibodies like trastuzumab have revolutionized the treatment of HER2-positive breast cancer by selectively targeting the HER2 receptor on cancer cells, leading to improved outcomes and reduced side effects. , …”

Section: Overview Of Colorectal Cancer and Precision Medicinementioning

confidence: 99%

See 1 more Smart Citation

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

Kiran,

Yashaswini,

Maheshwari

et al. 2024

ACS Pharmacol. Transl. Sci.

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Precision medicine is transforming colorectal cancer treatment through the integration of advanced technologies and biomarkers, enhancing personalized and effective disease management. Identification of key driver mutations and molecular profiling have deepened our comprehension of the genetic alterations in colorectal cancer, facilitating targeted therapy and immunotherapy selection. Biomarkers such as microsatellite instability (MSI) and DNA mismatch repair deficiency (dMMR) guide treatment decisions, opening avenues for immunotherapy. Emerging technologies such as liquid biopsies, artificial intelligence, and machine learning promise to revolutionize early detection, monitoring, and treatment selection in precision medicine. Despite these advancements, ethical and regulatory challenges, including equitable access and data privacy, emphasize the importance of responsible implementation. The dynamic nature of colorectal cancer, with its tumor heterogeneity and clonal evolution, underscores the necessity for adaptive and personalized treatment strategies. The future of precision medicine in colorectal cancer lies in its potential to enhance patient care, clinical outcomes, and our understanding of this intricate disease, marked by ongoing evolution in the field. The current reviews focus on providing in-depth knowledge on the various and diverse approaches utilized for precision medicine against colorectal cancer, at both molecular and biochemical levels.

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Section: Overview Of Colorectal Cancer and Precision Medicinementioning

confidence: 99%

Section: Overview Of Colorectal Cancer and Precision Medicinementioning

confidence: 99%

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

Kiran,

Yashaswini,

Maheshwari

et al. 2024

ACS Pharmacol. Transl. Sci.

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“…The emergence of genome‐driven precision oncology has transformed the treatment of numerous types of cancer and has also led us into a new era of tissue‐agnostic precision medicine 1 . Neurotrophic receptor tyrosine kinase (NTRK) inhibitors are a class of targeted therapies that specifically target and inhibit the activity of NTRKs 2 .…”

Section: Actionable Target Drug Mechanism Fda‐approved Tumor Type(s)mentioning

confidence: 99%

TRKing sarcomas for precision medicine: Seek, and ye shall find!

Moyers,

Subbiah

2023

Cancer

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Plain language summary The way in which we treat different types of cancer has changed a lot because of genome‐driven precision oncology. This approach uses information from a person’s genes to personalize their treatment. A recent study conducted by Kummar and colleagues confirms that neurotrophic receptor tyrosine kinase (NTRK) inhibitors are beneficial in treating sarcomas with NTRK fusions. This study adds to the growing evidence that genomics, which is the study of genes and their functions, can help us to identify effective treatments even for rare targets such as NTRK fusions. This emphasizes the importance of using advanced DNA sequencing techniques in analyzing the genetic makeup of all sarcomas.

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“…NTRK fusions affect only 0.31% of adult tumors and 0.34% of pediatric tumors. 20,21 However, they are highly actionable. Larotrectinib tumors with TRK fusions, regardless of tumor histology or anatomic location.…”

Section: Loxo-trk/scout/navigate/startrk Trials For Targeting Ntrk Fu...mentioning

confidence: 99%

Revolutionizing cancer drug development: Harnessing the potential of basket trials

Subbiah,

Burris,

Kurzrock

2023

Cancer

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The landscape of cancer therapy has been transformed by advances in clinical next‐generation sequencing, genomically targeted therapies, and immunotherapies. Well designed clinical trials and efficient clinical trial conduct are crucial for advancing our understanding of cancer, improving patient outcomes, and identifying personalized treatments. Basket trials have emerged as one of the efficient modern clinical trial designs that evaluate the efficacy of these therapies across multiple cancer types based on specific molecular alterations or biomarkers, irrespective of histology or anatomic location. This review delves into the evolution of basket trials in cancer drug development, highlighting their potential prospects and current obstacles. The design of basket trials involves screening patients for specific molecular alterations or biomarkers and enrolling them in the trial to receive the targeted therapy under investigation. Statistical considerations play a crucial role in the design, analysis, and interpretation of basket trials. Several notable examples of basket trials that have led to US Food and Drug Administration approval for uncommon molecular alterations (e.g., NTRK fusions, BRAF mutations, RET and FGFR1 alterations) are discussed, including LOXO‐TRK (ClinicalTrials.gov identifier NCT02122913)/SCOUT (ClinicalTrials.gov identifier NCT02637687)/NAVIGATE (ClinicalTrials.gov identifier NCT02576431)/STARTRK (ClinicalTrials.gov identifiers NT02097810, NT02568267), VE‐BASKET (ClinicalTrials.gov identifier NCT01524978), ROAR Basket (ClinicalTrials.gov identifier NCT02034110), LIBRETTO‐001 (ClinicalTrials.gov identifier NCT03157128), ARROW (ClinicalTrials.gov identifier NCT03037385), FIGHT‐203 (ClinicalTrials.gov identifier NCT03011372), and the National Cancer Institute‐Molecular Analysis for Therapy Choice trial (ClinicalTrials.gov identifier NCT02465060). Basket trials have the potential to revolutionize cancer treatment by identifying effective therapies for patients based on specific molecular alterations or biomarkers rather than traditional histology‐based approaches.Plain Language Summary To gain more knowledge about cancer, improve patient outcomes, and discover personalized treatments, it is crucial to conduct clinical trials efficiently. One effective type of clinical trial is called a basket trial. In basket trials, new treatments are tested on various types of cancer, regardless of their location in the body; instead, researchers focus on specific abnormalities in the cancer cells. Basket trials offer hope that we can find personalized treatments that are more effective for each individual battling cancer.

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Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications

Cited by 28 publications

References 86 publications

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

TRKing sarcomas for precision medicine: Seek, and ye shall find!

Revolutionizing cancer drug development: Harnessing the potential of basket trials

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