A Milestone in Advancing Cancer Care: 1,000 Peer-Reviewed Publications and Counting
Foundation Medicine recently hit an important milestone of more than 1,000 peer-reviewed publications,1,2 across esteemed journals such as The Lancet and The New England Journal of Medicine. This milestone is more than just a number – it reinforces our commitment to transforming cancer care through transparency, scientific excellence and rigorous, high-quality research.
For more than a decade, Foundation Medicine has worked with leading research institutions, healthcare providers, community networks and practices, scientists and biopharmaceutical partners to publish peer-reviewed studies that validate our portfolio of high-quality comprehensive genomic profiling (CGP) tests and help advance the field of biomarker testing.3 With every piece of peer-reviewed research, we have broadened our understanding of cancer as a disease and contributed to the body of knowledge demonstrating the benefits of precision medicine for cancer care.
While it is impossible to highlight every peer-reviewed publication (though you can view them all in our Resource Center), we want to reflect on eight key areas where Foundation Medicine’s research has had a lasting impact.
1. Identifying novel biomarkers and biomarker associations
A cornerstone of our research has been, and continues to be, the exploration, discovery, and validation of novel cancer drivers.
Leveraging our unique real-world, de-identified genomic data from the Foundation Medicine-Flatiron Clinico-Genomic Database (CGDB), we have identified novel biomarkers and biomarker associations that better shape our understanding of cancer as a disease. Additionally, with each discovery, we provide biopharmaceutical partners and clinical trialists with potential new biomarkers to target as they develop new therapy options.
Some examples of our contributions include:
- The discovery of new splicing sites associated with MET exon 14 as an oncogenic driver and potential therapeutic target,4 which later helped support the approval of capmatinib for MET exon 14-mutation non-small cell lung cancer5,6
- The discovery of tumor mutational burden (TMB) as a pan-tumor complex biomarker, solidifying TMB as a biomarker detectable by next-generation sequencing (NGS)7 and later helped support the approval of pembrolizumab in patients with TMB-high across solid tumor types8,9
- The identification of ALK and RET gene fusions in colorectal cancer and lung cancer10
- The identification of a new pan-cancer copy number loss homologous recombination deficiency signature known as HRDsig11
2. Pioneering liquid biopsy for biomarker detection
Foundation Medicine was an early pioneer of liquid biopsy. FoundationOne®Liquid CDx12 was among the first FDA-approved liquid biopsy NGS companion diagnostic tests.13
Unlike traditional tissue biopsies, liquid biopsies use a simple blood draw to analyze tiny amounts of circulating tumor DNA (ctDNA) that are shed from a tumor into the bloodstream to detect possible genomic alterations.
As an early innovator of blood-based biomarker testing, Foundation Medicine has shed light on the incredible value liquid biopsy can play in cancer care, including:
- How our liquid-based biomarker testing has a high success rate equivalent to tissue-based biomarker testing across tumor types14
- When to use liquid biopsy versus when to use tissue biopsy for the detection of actionable genomic alterations15
- The ability of our well-designed, high-quality liquid biopsy to detect actionable gene fusions, including kinase fusions, across tumor types16,17
- The ability of our high-quality liquid biopsy to detect acquired resistance alterations across lines of treatment in metastatic breast cancer18
- How early liquid biopsy in parallel with routine diagnostic work-up can shorten the time to targeted therapy initiation19
3. Defining the critical role of tumor fraction in liquid biopsies
As liquid biopsies play a larger role in cancer care and present a complementary approach to tissue-based biomarker testing, we have gained more insight into the various uses of ctDNA to help guide clinical care decisions.
For example, Foundation Medicine developed a new biomarker for liquid biopsies called ctDNA tumor fraction (ctDNA TF), a determination of the amount of ctDNA as a fraction of total cell-free DNA. Here are a few pieces of research highlighting the role played by ctDNA tumor fraction in liquid biopsies, including:
- The relationship between ctDNA tumor fraction and the detection of actionable alterations across cancer types20
- The utility of ctDNA tumor fraction in interpreting negative liquid biopsy results and informing when to follow up liquid biopsy testing with confirmatory tissue testing21
- The role of ctDNA tumor fraction as an independent prognostic biomarker across four common advanced cancers22
- The value of serial ctDNA tumor fraction monitoring as a complement to PSA testing to measure treatment response in metastatic castration-resistant prostate cancer23
4. Advancing our understanding of acquired alterations that cause therapeutic resistance
Thanks to the discovery of more actionable biomarkers, patients have more targeted treatment options available that are tailored to the unique alterations present in their cancer. Unfortunately, cancers can acquire additional mutations that cause treatment resistance and disease progression.
Over the years, Foundation Medicine has made significant contributions to advancing our understanding of resistance mechanisms in cancers such as non-small cell lung cancer (NSCLC), breast cancer and ovarian cancer, including:
- Examining EGFR second site mutations and other resistance mechanisms to osimertinib in NSCLC24
- Identifying ESR1 mutations that led to endocrine resistance in metastatic breast cancer25
- Advancing the understanding of the diverse genomic and histologic mechanisms of resistance to KRAS inhibitors26
- Evaluating secondary reversion mutations outside of BRCA1/2 that cause resistance to PARP inhibitor usage in ovarian cancer27
Understanding what alterations may drive a patient’s resistance to treatment is vital in helping healthcare providers make informed decisions on the next-line treatment options. As we have learned more about acquired mutations, the evidence needed for biomarker testing at the time of disease progression continues to grow.
5. Exploring the role of comprehensive genomic profiling in rare cancers
Rare cancers, as a group, account for a quarter of all cancers and a quarter of all cancer deaths.28 However, diagnosing and treating rare cancers, such as cancer of unknown primary (CUP), can be challenging given the diversity of the disease and the small patient population for each.
Hematological cancers, including leukemia, lymphoma and myeloma, account for around 10% of new cancer diagnoses in the U.S. each year.29 But with a limited number of targeted treatment options available, biomarker testing for hematological malignancies has lagged behind other tumor types.
With genomic data on a broad array of cancers available through the CGDB, Foundation Medicine is uniquely positioned to explore the potential genomic drivers behind these cancers, as well as identify possible opportunities where biomarker testing can help guide treatment decisions, shining a light on areas such as:
- The role of CGP testing in guiding treatment decisions for CUP patients, demonstrating the progression-free survival benefit of molecularly guided therapy for CUP patients30
- The role of CGP in identifying clinically actionable alterations in patients with rare or refractory cancers31
- How an integrated DNA/RNA next-generation sequencing assay can identify genomic mutations for patients with hematological malignancies32
- The role that CGP can play in guiding and advancing targeted acute myeloid leukemia treatment options33
6. Evaluating real-world outcomes to help inform treatment selection
As more targeted therapies come to market, evaluating real-world outcomes can refine biomarker selection by identifying additional biomarkers that may be actionable or those associated with resistance. Armed with this information, healthcare providers can make more informed decisions on the best possible treatment options for their patients.
Foundation Medicine has frequently contributed to outcome studies to aid with treatment selection, particularly when it comes to advancing our understanding of biomarkers that can inform the use of immune checkpoint inhibitors and PARP inhibitors.
To aid healthcare providers in understanding what biomarkers may signal benefit or resistance to immune checkpoint inhibitors, Foundation Medicine has made significant contributions, including:
- Evaluating the role of PD-L1 expression and TMB as independent biomarkers that may inform immune checkpoint inhibitor response34
- Identifying STK11/LKB1 mutations as a prevalent genomic driver of resistance to PD-1 inhibitors in KRAS-mutant lung adenocarcinoma35
- Demonstrating that elevated TMB is associated with more favorable overall survival on immune checkpoint inhibitors across solid tumor types36
For PARP inhibitor use, Foundation Medicine’s peer-reviewed publications have shed light on:
- How biallelic BRCA1/2 loss confers a strong response to PARP inhibitors37
- The prevalence of biallelic loss of PALB2 and potential responsiveness to PARP inhibitors38
- The role of loss of heterozygosity in identifying patients who may benefit from PARP inhibitor use39
- How a scar-based HRD signature can offer a new approach to identifying patients who may benefit from PARP inhibitors, even for those without BRCA1/2 alterations40
7. Supporting biopharmaceutical partners with clinical trials and companion diagnostic development
Foundation Medicine is the global leader in approved companion diagnostic indications, with 50% of all companion diagnostic indications for next-generation sequencing testing across the U.S. and Japan.41
With our proven regulatory, clinical trial and companion diagnostic development expertise, along with the strength of our CGDB, biopharmaceutical partners trust us to support the development of their investigational therapies and the accompanying companion diagnostic. Over the years, Foundation Medicine has supported more than 950 clinical trials, including over 350 prospective trials.42
Here is a sampling of the peer-reviewed publications we have contributed to with our biopharmaceutical partners in support of their clinical trial work and the development of companion diagnostic tests:
- Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib)43
- Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial5
- Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study8
- Validation and Characterization of FGFR2 Rearrangements in Cholangiocarcinoma with Comprehensive Genomic Profiling44
- Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population45
8. Addressing the need for timely access to biomarker testing for all people living with cancer
All people living with cancer deserve timely access to high-quality biomarker tests to make precise and personalized treatment decisions based on the unique characteristics of their cancer.
Through close collaborations with our partners across the oncology community, Foundation Medicine has worked to expand access to high-quality biomarker testing through our grant program and close collaboration with payers. With our research, we have also highlighted the benefit timely access to biomarker testing has on patient outcomes, including:
- Demonstrating how biomarker testing in early-stage lung cancer led to quicker treatment at recurrence and cost savings by avoiding ineffective treatment options46
- Illustrating how timely access to biomarker test results improved targeted therapy usage in the first-line setting and led to a longer time to therapy discontinuation47
A continued commitment to advancing cancer care
We are incredibly proud to surpass more than 1,000 peer-reviewed publications. This milestone is a true testament to the hard work and dedication of our team to transform cancer care and help every patient benefit from the advances in precision oncology.
We are committed to continuing to advance research that we know will make a difference in the lives of the patients we support every day. With a portfolio of high-quality biomarker tests, Foundation Medicine is well-positioned to continue to generate important real-world genomic data that can help uncover new biomarkers, advance the development of new targeted treatment options, and reshape our understanding of cancer as a disease.
References
1 Data on File, Foundation Medicine, Inc., 2024
2 Manuscripts indexed in PubMed
3 Frampton GM, Fichtenholtz A, Otto GA, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013;31(11):1023-1031. https://doi.org/10.1038/nbt.2696
4 Frampton GM, Ali SM, Rosenzweig M, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015;5(8):850-9. https://doi.org/10.1158/2159-8290.CD-15-0285
5 Wolf J, Hochmair M, Han JY, et al. Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from open-label, phase 2 GEOMETRY mono-1 trial. Lancet Oncol. 2024;25(10):1357-1370. https://doi.org/10.1016/s1470-2045(24)00441-8
6 Foundation Medicine. Foundation Medicine Receives FDA Approval for FoundationOne®CDx as the Companion Diagnostic for Tabrecta™ (capmatinib), the Only FDA-Approved MET Inhibitor for Patients With Metastatic Non-Small Cell Lung Cancer With METex14. Created March 7, 2020. Accessed January 27, 2025. https://www.foundationmedicine.com/press-releases/foundation-medicine-receives-fda-approval-for-foundationone%C2%AEcdx-as-the-companion-diagnostic-for-tabrecta%E2%84%A2-%28capmatinib%29%2C-the-only-fda-approved-met-inhibitor-for-patients-with-metastatic-non-small-ce
7 Chalmers ZR, Connelly CF, Fabrizio D, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9(1):34. https://doi.org/10.1186/s13073-017-0424-2
8 Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21(10):1352-1365. https://doi.org/10.1016/s1470-2045(20)30445-9
9 Foundation Medicine. FoundationOne®CDx Receives FDA Approval as the First Companion Diagnostic to Identify Advanced Cancer Patients with Solid Tumors that are Tumor Mutational Burden-High (TMB-H) and Appropriate for Immunotherapy Treatment with KEYTRUDA® (pembrolizumab). Created June 18, 2020. Accessed January 27, 2025. https://www.foundationmedicine.com/press-releases/foundationone%C2%AEcdx-receives-fda-approval-as-the-first-companion-diagnostic-to-identify-advanced-cancer-patients-with-solid-tumors-that-are-tumor-mutational-burden-high-%28tmb-h%29-and-appropriate-for-immu
10 Lipson D, Capelletti M, Yelensky R, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012;18(3):382-4. https://doi.org/10.1038/nm.2673
11 Moore JA, Kuei-Ting C, Madison R, et al. Pan-cancer analysis of copy-number features identifies recurrent signatures and a homologous recombination deficiency biomarker to predict poly (ADP-ribose) polymerase inhibitor response. JCO Precis Oncol. 2023;7. https://doi.org/10.1200/PO.23.00093
12 FoundationOne®Liquid CDx is for prescription use only and is a qualitative next-generation sequencing based in vitro diagnostic test for advanced cancer patients with solid tumors. The test analyzes 324 genes utilizing circulating cell-free DNA and is FDA-approved to report short variants in 311 genes and as a companion diagnostic to identify patients who may benefit from treatment with specific therapies (listed in Table 1 of the Intended Use) in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. When considering eligibility for ROZLYTREK® based on the detection of NTRK1/2/3 and ROS1 fusions, or for TEPMETKO® based on the detection of MET SNVs and indels that lead to MET exon 14 skipping, testing using plasma specimens is only appropriate for patients for whom tumor tissue is not available for testing. Patients who are negative for other companion diagnostic mutations should be reflexed to tumor tissue testing and mutation status confirmed using an FDA-approved tumor tissue test, if feasible. For the complete label, including companion diagnostic indications and complete risk information, please visit www.F1LCDxLabel.com.
13 National Cancer Institute. FDA Approves Blood Tests That Can Help Guide Cancer Treatment. Published October 15, 2020. Accessed January 2, 2025. https://www.cancer.gov/news-events/cancer-currents-blog/2020/fda-guardant-360-foundation-one-cancer-liquid-biopsy
14 Lin DI, Pasquina LW, Mavares E, Elvin JA, Huang RSP. Real-world pan-tumor comprehensive genomic profiling sample adequacy and success rates in tissue and liquid specimens. Oncologist. 2025;30(20):oyae258. https://doi.org/10.1093/oncolo/oyae258
15 Schwartzberg LS, Li G, Tolba K, et al. Complementary roles for tissue- and blood-based comprehensive genomic profiling for detection of actionable driver alterations in advanced NSCLC. JTO Clin Res Rep. 2022;3(9):100386. https://doi.org/10.1016/j.jtocrr.2022.100386
16 Kasi PM, Lee JK, Pasquina LW, et al. Circulating tumor DNA enables sensitive detection of actionable gene fusions and rearrangements across cancer types. Clin Cancer Res. 2024; 30(4):836-848. https://doi.org/10.1158/1078-0432.ccr-23-2693
17 Lee JK, Hazar-Rethinam M, Decker B, et al. The pan-tumor landscape of targetable kinase fusions in circulating tumor DNA. 2022;28(4):728-737. Clin Cancer Res. https://doi.org/10.1158/1078-0432.ccr-21-2136
18 Bhave MA, Quintanilha JCF, Tukachinsky H, et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res Treat. 2024;207(3);599-609. https://doi.org/10.1007/s10549-024-07376-w
19 Russo A, Lee JK, Pasquina LW, et al. Liquid biopsy of lung cancer before pathological diagnosis is associated with shorter time to treatment. JCO Precis Oncol. 2024;8:e2300535. https://doi.org/10.1200/po.23.00535
20 Husain H, Pavlick DC, Fendler BJ, et al. Tumor fraction correlates with detection of actionable variants across > 23,000 circulating tumor DNA samples. JCO Precis Oncol. 2022;6. https://doi.org/10.1200/po.22.00261
21 Rolfo CD, Madison RW, Pasquina LW, et al. Measurement of ctDNA tumor fraction identifies informative negative liquid biopsy results and informs value of tissue confirmation. Clin Cancer Res. 2024;30(11):2452-2460. https://doi.org/10.1158/1078-0432.ccr-23-3321
22 Reichert ZR, Morgan TM, Li G, et al. Prognostic value of plasma circulating tumor DNA fraction across four common cancer types: a real-world outcomes study. Ann Oncol. 2023; 34(1):111-120. https://doi.org/10.1016/j.annonc.2022.09.163
23 Sweeney CJ, Petry R, Xu C, et al. Circulating tumor DNA assessment for treatment monitoring adds value to PSA in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2024;30(18):4115-4122. https://doi.org/10.1158/1078-0432.ccr-24-1096
24 Rotow JK, Lee JK, Madison RW, Oxnard GR, Jänne PA, Schrock AB. Real-world genomic profile of EGFR second-site mutations and other Osimertinib resistance mechanisms and clinical landscape of NSCLC post-osimertinib. J Thorac Oncol. 2024;19(2):227-239. https://doi.org/10.1016/j.jtho.2023.09.1453
25 Merenbakh-Lamin K, Ben-Baruch N, Yekeskel A, et al. D538G mutations in estrogen receptor-α: a novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res. 2013;73(23):6856-64. https://doi.org/10.1158/0008-5472.can-13-1197
26 Awad MM, Lieu S, Rybkin II, et al. Acquired resistance to KRASG12C inhibition in cancer. N Engl J Med. 2021;384(24):2382-2393. https://doi.org/10.1056/nejmoa2105281
27 Kondrashova O, Nguygen M, Shield-Artin K, et al. Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma. Cancer Discov. 2017;7(9):984-998. https://doi.org/10.1158/2159-8290.cd-17-0419
28 National Cancer Institute. About Rare Cancers. Published February 27, 2019. Accessed January 2, 2025. https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/about-rare-cancers
29 The Leukemia & Lymphoma Society. Facts 2023-2024. Updated Data on Blood Cancers. Published August 2024. Accessed November 22, 2024. https://lls.org/booklet/facts-updated-data-blood-cancers
30 Krämer A, Bochtler T, Pauli C, et al. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomized, phase 2 study. Lancet. 2024;404(10452):527-539. https://doi.org/10.1016/s0140-6736(24)00814-6
31 Hirshfield KM, Tolkunov D, Zhong H, et al. Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers. Oncologist. 2016;21(11):1315-1325. https://doi.org/10.1634/theoncologist.2016-0049
32 He J, Abdel-Wahab O, Nahas MK, et al. Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting. Blood. 2016;127(24):3004-14. https://doi.org/10.1182/blood-2015-08-664649
33 Burd A, Levine RL, Ruppert AS, et al. Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. Nat Med. 2020;26(12):1852-1858. https://doi.org/10.1038/s41591-020-1089-8
34 Yarchoan M, Albacker LA, Hopkins AC, et al. PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers. JCI Insight. 2019;4(6). https://doi.org/10.1172/jci.insight.126908
35 Skoulidis F, Goldberg ME, Greenawalt DM, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 2018;8(7):822-835. https://doi.org/10.1158/2159-8290.cd-18-0099
36 Gandara DR, Agarwal N, Gupta S, et al. Tumor mutational burden and survival on immune checkpoint inhibition in >8000 patients across 24 cancer types. J Immunother Cancer. 2025;13(2):e010311. https://doi.org/10.1136/jitc-2024-010311
37 Triner D, Graf RP, Madison RW, et al. Durable benefit from poly(ADP-ribose) polymerase inhibitors in metastatic prostate cancer in routine practice: biomarker associations and implications for optimal clinical next-generation sequencing test. ESMO Open. 2024;9(9):103684. https://doi.org/10.1016/j.esmoop.2024.103684
38 Bhangoo MS, Constantini C, Clifford BT, et al. Biallelic deletion of PALB2 occurs across multiple tumor types and suggests responsiveness to poly (ADP-ribose) polymerase inhibition. JCO Precis Oncol. 2017;1:1-7. https://doi.org/10.1200/po.17.00043
39 Swisher EM, Lin KK, Oza AM, et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017; 18(1):75-87. https://doi.org/10.1016/s1470-2045(16)30559-9
40 Richardson DL, Quintanilha JCF, Danzinger, et al. Effectiveness of PARP inhibitor maintenance therapy in ovarian cancer by BRCA1/2 and a scar-based HRD signature in real-world practice. Clin Cancer Res. 2024;30(20):4644-4653. https://doi.org/10.1158/1078-0432.ccr-24-1225
41 Data on File, Foundation Medicine, Inc., data as of November 2024.
42 Data on File, Foundation Medicine, Inc., 2024.
43 Hussain M, Corcoran C, Sibilla C, et al. Tumor genomic testing for >4,000 men with metastatic castration-resistant prostate cancer in the phase III trial PROfound (olaparib). Clin Cancer Res. 2022;28(8):1518-1530. https://doi.org/10.1158/1078-0432.ccr-21-3940
44 Silverman IM, Li M, Murugesan K, et al. Validation and characterization of FGFR2 rearrangements in cholangiocarcinoma with comprehensive genomic profiling. J Mol Diagn. 2022;24(4):351-364. https://doi.org/10.1016/j.jmoldx.2021.12.012
45 Westphalen CB, Krebs MG, Le Tourneau C, et al. Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population. NPJ Precis Oncol. 2021;5(1):69. https://doi.org/10.1038/s41698-021-00206-y
46 Muthusamy B, Raskina K, Lofgren KT, et al. Quantifying the value of multigene testing in resected early stage lung adenocarcinoma. J Thorac Oncol. 2023;18(4):476-486. https://doi.org/10.1016/j.jtho.2022.11.027
47 Yorio J, Lofgren KT, Lee JK, et al. Association of timely comprehensive genomic profiling with precision oncology treatment use and patient outcomes in advanced non-small-cell lung cancer. JCO Precis Oncol. 2024;8. https://doi.org/10.1200/po.23.00292