Dr. Chen is a board-certified, fellowship-trained specialist in oncology and hematology. He is also an Assistant Professor in the Division of Oncology in the Department of Medicine at Stanford University School of Medicine.
Dr. Chen delivers comprehensive, compassionate care for patients in need of early drug development clinical trials and patients with gastrointestinal cancers. As a researcher, he leads the early drug development group and studies how tumor heterogeneity limits the clinical benefit of anticancer therapies in order to accelerate development of novel therapeutic strategies. Dr. Chen’s work has appeared in the New England Journal of Medicine, JAMA, Journal of Clinical Oncology, Science Advances, Journal of Oncology Practice, and Health Services Research.
Dr. Chen attended Harvard College, where he graduated summa cum laude and Phi Beta Kappa in molecular biology. He went to medical school at Washington University in St. Louis on a full-tuition merit scholarship, graduating with Alpha Omega Alpha honors, and did his residency training in internal medicine at Massachusetts General Hospital and hematology/oncology fellowship in the combined Harvard Dana-Farber Cancer Institute/Massachusetts General Hospital program. As a fellow, he received the NIH T-32 Ruth L. Kirchstein-National Service Research Award in Cancer Biology for his work exploring the molecular structure of metastatic solid tumors.
Dr. Chen is a member of the American Society of Clinical Oncology and European Society for Medical Oncology. He is an associate member of the American Association for Cancer Research.
- Developmental Therapeutics
- GI Oncology
- Internal Medicine
Assistant Professor - University Medical Line, Medicine - Oncology
Clinical Director, Early Drug Development, Stanford Cancer Institute (2021 - Present)
Honors & Awards
Andrea Lynn Scott Memorial Research Fellowship, Cholangiocarcinoma Foundation (2021-2022)
FDA-AACR Oncology Education Fellow, FDA / AACR (2020-2021)
T32 Ruth L. Kirschstein-National Service Research Award in Cancer Biology, NIH (2018-2020)
Board Certification, American Board of Internal Medicine, Medical Oncology (2020)
Fellowship: Dana Farber Cancer Institute Hematology Oncology Fellowship (2020) MA
Board Certification: American Board of Internal Medicine, Internal Medicine (2017)
Residency: Massachusetts General Hospital Internal Medicine Residency (2017) MA
Medical Education: Washington University in St Louis Registrar (2014) MO
BA, Harvard College, Molecular Biology, Economics, Health Policy (2010)
- Paving a pathway for drug development in HER2-positive biliary tract cancer. The Lancet. Oncology 2021; 22 (9): 1204-1206
- Case 8-2021: A 34-Year-Old Woman with Cholangiocarcinoma. The New England journal of medicine 2021; 384 (11): 1054–64
Cell-free DNA captures tumor heterogeneity and driver alterations in rapid autopsies with pre-treated metastatic cancer.
2021; 12 (1): 3199
In patients with metastatic cancer, spatial heterogeneity of somatic alterations may lead to incomplete assessment of a cancer's mutational profile when analyzing a single tumor biopsy. In this study, we perform sequencing of cell-free DNA (cfDNA) and distinct metastatic tissue samples from ten rapid autopsy cases with pre-treated metastatic cancer. We show that levels of heterogeneity in genetic biomarkers vary between patients but that gene expression signatures representative of the tumor microenvironment are more consistent. Across nine patients with plasma samples available, we are able to detect 62/62 truncal and 47/121 non-truncal point mutations in cfDNA. We observe that mutation clonality in cfDNA is correlated with the number of metastatic lesions in which the mutation is detected and use this result to derive a clonality threshold to classify truncal and non-truncal driver alterations with reasonable specificity. In contrast, mutation truncality is more often incorrectly assigned when studying single tissue samples. Our results demonstrate the utility of a single cfDNA sample relative to that of single tissue samples when treating patients with metastatic cancer.
View details for DOI 10.1038/s41467-021-23394-4
View details for PubMedID 34045463
Overcoming Resistance to Targeted Therapies in Gastrointestinal Cancers: Progress to Date and Progress to Come.
American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
2020; 40: 161–73
Targeted therapies have transformed the treatment paradigm in diseases such as non-small cell lung cancer and melanoma but have shown relatively modest clinical benefit in gastrointestinal malignancies. Anti-EGFR therapy in RAS wild-type colorectal cancer, anti-HER2 therapy in HER2- amplified esophagogastric cancer, and FGFR and isocitrate dehydrogenase 1 (IDH1) inhibitors in FGFR2 fusion-positive and IDH1-mutant biliary tract cancers offer antitumor efficacy, but the clinical benefit and durability of response in each case are typically limited. We review targeted therapies in each of these therapeutic areas and discuss their clinical efficacy, mechanisms of primary and acquired resistance, and strategies to overcome this resistance. We discuss lessons learned that we hope will lead to an expanded role for molecularly targeted therapy options for patients with gastrointestinal cancers.
View details for DOI 10.1200/EDBK_280871
View details for PubMedID 32421451
Response rates and lesion-level progression patterns of solid tumor patients in an academic phase I program: implications for tumour heterogeneity
OXFORD UNIV PRESS. 2019
View details for Web of Science ID 000491295501307
Pharmacological inhibition of β-catenin/BCL9 interaction overcomes resistance to immune checkpoint blockades by modulating Treg cells.
2019; 5 (5): eaau5240
The Wnt/β-catenin (β-cat) pathway plays a critical role in cancer. Using hydrocarbon-stapled peptide technologies, we aim to develop potent, selective inhibitors targeting this pathway by disrupting the interaction of β-cat with its coactivators B-cell lymphoma 9 (BCL9) and B-cell lymphoma 9-like (B9L). We identified a set of peptides, including hsBCL9CT-24, that robustly inhibits the activity of β-cat and suppresses cancer cell growth. In animal models, these peptides exhibit potent anti-tumor effects, favorable pharmacokinetic profiles, and minimal toxicities. Markedly, these peptides promote intratumoral infiltration of cytotoxic T cells by reducing regulatory T cells (Treg) and increasing dendritic cells (DCs), therefore sensitizing cancer cells to PD-1 inhibitors. Given the strong correlation between Treg infiltration and APC mutation in colorectal cancers, it indicates our peptides can reactivate anti-cancer immune response suppressed by the oncogenic Wnt pathway. In summary, we report a promising strategy for cancer therapy by pharmacological inhibition of the Wnt/β-cat signaling.
View details for DOI 10.1126/sciadv.aau5240
View details for PubMedID 31086813
View details for PubMedCentralID PMC6506245
Efficacy, Safety, and Regulatory Approval of Food and Drug Administration-Designated Breakthrough and Nonbreakthrough Cancer Medicines.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2018; 36 (18): 1805–12
Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non-breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non-breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression. Results Between 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non-breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non-breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy-designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non-breakthrough-designated drugs. Conclusion Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy advantage when compared with non-breakthrough-designated drugs.
View details for DOI 10.1200/JCO.2017.77.1592
View details for PubMedID 29688832
Medicare Spending for Breast, Prostate, Lung, and Colorectal Cancer Patients in the Year of Diagnosis and Year of Death.
Health services research
2018; 53 (4): 2118–32
To characterize spending patterns for Medicare patients with incident breast, prostate, lung, and colorectal cancer.2007-2012 data from the Surveillance, Epidemiology, and End Results Program linked with Medicare fee-for-service claims.We calculate per-patient monthly and yearly mean and median expenditures, by cancer type, stage at diagnosis, and spending category, over the years of diagnosis and death.Over the year of diagnosis, mean spending was $35,849, $26,295, $55,597, and $63,063 for breast, prostate, lung, and colorectal cancer, respectively. Over the year of death, spending was similar across different cancer types and stage at diagnosis.Characterization of Medicare spending according to clinically meaningful categories may assist development of oncology alternative payment models and cost-effectiveness models.
View details for DOI 10.1111/1475-6773.12745
View details for PubMedID 28748564
View details for PubMedCentralID PMC6051983
Walk-in clinics versus physician offices and emergency rooms for urgent care and chronic disease management.
Cochrane database of systematic reviews
2017; 2: CD011774-?
Walk-in clinics are growing in popularity around the world as a substitute for traditional medical care delivered in physician offices and emergency rooms, but their clinical efficacy is unclear.To assess the quality of care and patient satisfaction of walk-in clinics compared to that of traditional physician offices and emergency rooms for people who present with basic medical complaints for either acute or chronic issues.We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers on 22 March 2016 together with reference checking, citation searching, and contact with study authors to identify additional studies. We applied no restrictions on language, publication type, or publication year.Study design: randomized trials, non-randomized trials, and controlled before-after studies.standalone physical clinics not requiring advance appointments or registration, that provided basic medical care without expectation of follow-up. Comparisons: traditional primary care practices or emergency rooms.We used standard methodological procedures expected by Cochrane and the Cochrane Effective Practice and Organisation of Care (EPOC) Group.The literature search identified 6587 citations, of which we considered 65 to be potentially relevant. We reviewed the abstracts of all 65 potentially relevant studies and retrieved the full texts of 12 articles thought to fit our study criteria. However, following independent author assessment of the full texts, we excluded all 12 articles.Controlled trial evidence about the mortality, morbidity, quality of care, and patient satisfaction of walk-in clinics is currently not available.
View details for DOI 10.1002/14651858.CD011774.pub2
View details for PubMedID 28211045
- Journey of Generic Imatinib: A Case Study in Oncology Drug Pricing. Journal of oncology practice 2017; 13 (6): 352–55
Transforming healthcare delivery: Why and how accountable care organizations must evolve.
Journal of hospital medicine
2016; 11 (9): 658–61
Accountable care organizations (ACOs) have shown promise in reducing healthcare spending growth, but have proven to be financially unsustainable for many healthcare organizations. Even ACOs with shared savings have experienced overall losses because the shared savings bonuses have not covered the costs of delivering population health. As physicians and former ACO leaders, we believe in the concept of accountable care, but ACOs need to evolve if they are to have a viable future. We propose the novel possibility of allowing ACOs to bill fee-for-service for their population health interventions, a concept we call population health billing. Journal of Hospital Medicine 2016;11:658-661. © 2016 Society of Hospital Medicine.
View details for DOI 10.1002/jhm.2589
View details for PubMedID 27596543
Disruptive innovation in academic medical centers: balancing accountable and academic care.
Academic medicine : journal of the Association of American Medical Colleges
2015; 90 (5): 594–98
Numerous academic medicine leaders have argued that academic referral centers must prepare for the growing importance of accountability-driven payment models by adopting population health initiatives. Although this shift has merit, execution of this strategy will prove significantly more problematic than most observers have appreciated. The authors describe how successful implementation of an accountable care health strategy within a referral academic medical center (AMC) requires navigating a critical tension: The academic referral business model, driven by tertiary-level care, is fundamentally in conflict with population health. Referral AMCs that create successful value-driven population health systems within their organizations will in effect disrupt their own existing tertiary care businesses. The theory of disruptive innovation suggests that balancing the push and pull of academic and accountable care within a single organization is achievable. However, it will require significant shifts in resource allocation and changes in management structure to enable AMCs to make the inherent difficult choices and trade-offs that will ensue. On the basis of the theories of disruptive innovation, the authors present recommendations for how academic health systems can successfully navigate these issues as they transition toward accountability-driven care.
View details for DOI 10.1097/ACM.0000000000000606
View details for PubMedID 25517702
Readmission penalties and health insurance expansions: a dispatch from Massachusetts.
Journal of hospital medicine
2014; 9 (11): 681–87
Payers are penalizing hospitals for high readmission rates. It is unknown whether major changes in population insurance coverage can affect readmission rates, despite the Affordable Care Act's coverage expansions coming into effect this year.To evaluate the impact of a large-scale insurance expansion on hospital readmissions, using Massachusetts' 2006 health reform as a natural experiment.Difference-in-difference time-series design.All Massachusetts acute-care hospitals.Inpatient visits from 2004 to 2010.Primary outcome was the hospital 30-day readmission rate. Readmissions to any Massachusetts hospital were tracked.Decreases in uninsurance rates during and after reform were largely limited to the hospital quartile with the highest prereform uninsurance rates (from 14% uninsured at the start of the reform to 2.9% by the end of the study period). The other hospitals collectively experienced a smaller decline in their uninsured admissions (5.9% at the start of reform to 2.5% by the end of the study period). According to difference-in-difference regression analysis, the highest uninsured hospital quartile experienced a modest increase in their unadjusted readmission rate of 0.6 percentage points (95% confidence interval: 0.1%-1.1%) during the reform period as compared to the other hospital quartiles (P = 0.01). This represents a relative increase of 4.5% in the readmission rate. Risk-adjusted readmission rates showed no corresponding change.The Affordable Care Act's insurance expansion may be associated with an increase in unadjusted readmission rates among hospitals that cared for disproportionate numbers of uninsured patients. Risk-adjustment appears to take this effect into account.
View details for DOI 10.1002/jhm.2213
View details for PubMedID 24945696
- Beyond ACOs and bundled payments: Medicare's shift toward accountability in fee-for-service. JAMA 2014; 311 (7): 673–74
- Massachusetts' health care reform and emergency department utilization. The New England journal of medicine 2011; 365 (12): e25