TY - JOUR
T1 - The Combiome Hypothesis
T2 - Selecting Optimal Treatment for Cancer Patients
AU - Hirsch, Fred R.
AU - Walker, Jill
AU - Higgs, Brandon W.
AU - Cooper, Zachary
AU - Raja, Rajiv G.
AU - Wistuba, Ignacio I.
N1 - Funding Information:
FRH has participated in scientific advisory boards for: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi, Genentech/Roche, Merck, Novartis, OncoCyte, Pfizer, Regeneron, Sanofi. FRH has had research funding through the University of Colorado to his lab from: Amgen, Abbvie, Bristol Myers Squibb, Celgene, Genentech, Lilly/ImClone, Rain Therapeutics, Mersana, Aurora Oncology, and Biodesix. FRH is an investigator in a University of Colorado-owned patent: “EGFR protein expression and EGFR high copy number as predictive biomarker for EGFR directed therapy.” JW and ZC are current employees and shareholders of AstraZeneca. RGR is a current employee and shareholder of AstraZeneca with a MedImmune (AstraZeneca company) patent pending related to blood tumor mutational burden. BWH was employed by AstraZeneca at the time of article development and is an AstraZeneca shareholder. IIW has provided consulting or advisory roles for AstraZeneca/MedImmune, Asuragen, Bayer, Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, Guardant Health, HTG Molecular Diagnostics, Merck, MSD Oncology, OncoCyte, Novartis, Flame Inc, and Pfizer; has received grants and personal fees from Asuragen, Genentech/Roche, Bristol Myers Squibb, AstraZeneca/MedImmune, HTG Molecular, Merck, and Guardant Health; has received personal fees from GlaxoSmithKline and Oncocyte, Daiichi-Sankyo, Roche, AstraZeeca, Pfizer and Bayer; has received research funding to his institution from 4D Molecular Therapeutics, Adaptimmune, Adaptive Biotechnologies, Akoya Biosciences, Amgen, Bayer, EMD Serono, Genentech, Guardant Health, HTG Molecular Diagnostics, Iovance Biotherapeutics, Johnson & Johnson, Karus Therapeutics, MedImmune, Merck, Novartis, OncoPlex Diagnostics, Pfizer, Silicon Biosytems, Takeda, and Novartis.
Funding Information:
Medical writing assistance was provided by Anne-Marie Manwaring, of Parexel (Worthing, UK) and was funded by AstraZeneca.
Publisher Copyright:
© 2021 The Author(s)
PY - 2022/1
Y1 - 2022/1
N2 - Existing approaches for cancer diagnosis are inefficient in the use of diagnostic tissue, and decision-making is often sequential, typically resulting in delayed treatment initiation. Future diagnostic testing needs to be faster and optimize increasingly complex treatment decisions. We envision a future where comprehensive testing is routine. Our approach, termed the “combiome,” combines holistic information from the tumor, and the patient's immune system. The combiome model proposed here advocates synchronized up-front testing with a panel of sensitive assays, revealing a more complete understanding of the patient phenotype and improved targeting and sequencing of treatments. Development and eventual adoption of the combiome model for diagnostic testing may provide better outcomes for all cancer patients, but will require significant changes in workflows, technology, regulations, and administration. In this review, we discuss the current and future testing landscape, targeting of personalized treatments, and technological and regulatory advances necessary to achieve the combiome.
AB - Existing approaches for cancer diagnosis are inefficient in the use of diagnostic tissue, and decision-making is often sequential, typically resulting in delayed treatment initiation. Future diagnostic testing needs to be faster and optimize increasingly complex treatment decisions. We envision a future where comprehensive testing is routine. Our approach, termed the “combiome,” combines holistic information from the tumor, and the patient's immune system. The combiome model proposed here advocates synchronized up-front testing with a panel of sensitive assays, revealing a more complete understanding of the patient phenotype and improved targeting and sequencing of treatments. Development and eventual adoption of the combiome model for diagnostic testing may provide better outcomes for all cancer patients, but will require significant changes in workflows, technology, regulations, and administration. In this review, we discuss the current and future testing landscape, targeting of personalized treatments, and technological and regulatory advances necessary to achieve the combiome.
KW - Antigenicity
KW - Co-stimulation
KW - Immune activation
KW - Immune checkpoint
KW - Targeted therapies
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U2 - 10.1016/j.cllc.2021.08.011
DO - 10.1016/j.cllc.2021.08.011
M3 - Review article
C2 - 34645581
AN - SCOPUS:85116906027
SN - 1525-7304
VL - 23
SP - 1
EP - 13
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 1
ER -