BACKGROUND
The MAPK (mitogen-activated protein kinsase) pathway is frequently activated in different cancers. Inhibitors of different molecules across this pathway have been developed for cancer treatment, including BRAF (B-Raf proto-oncogene, serine/threonine kinase), MEK (mitogen-activated protein kinase), and ERK (extracellular signal-regulated kinase) inhibitors.[1–3] The interplay between rat sarcoma (RAS) and downstream rapidly accelerated fibrosarcoma (RAF), MEK, and ERK has been commonly noted, although conclusions about their relationship are still debatable. For example, data have shown that secondary cutaneous malignancies developing during BRAF inhibition might be driven by RAS alterations.[4] Moreover, RAS mutations have been described as possible mechanisms of resistance to combined BRAF and MEK inhibition.[5,6] In BRAF wild-type tumors, paradoxical activation of the RAF, MEK, and/or ERK pathway in a RAS-dependent manner leads to aberrant tumor growth and differentiation.[7–9] Limited data are available regarding response to BRAF, MEK, and ERK inhibitors in patients with upstream RAS alterations; although concerns about RAS-driven resistance to downstream MAPK inhibition are supported by prior research.[4,6,10]
Herein, we aimed to explore the possible associations between RAS status and clinical outcomes in patients with advanced cancers who had been treated with RAF, MEK, and ERK inhibitors. We hypothesized that RAS mutations would confer resistance to downstream MAPK pathway inhibition.
METHODS
This study was approved by the institutional review board at The University of Texas MD Anderson Cancer Center. In this retrospective study, we used The University of Texas MD Anderson Cancer Center CHIMERA platform to extract demographic and clinical data on patients with advanced solid tumors who had been treated with investigational protocols that included RAF, MEK, and/or ERK inhibitors as part of early-phase clinical trials in the Department of Investigational Cancer Therapeutics. Only patients who had undergone a next-generation sequencing test before enrollment were included. Patients who did not complete 30 days of therapy with RAF, MEK, and/or ERK inhibitors and those who were unevaluable for response were excluded from the analysis. We also excluded patients who received other drugs in combination treatment protocols that did not include RAF, MEK, and/or ERK inhibitors at cycle 1, day 1 (C1D1); patients who received nonselective RAF, MEK, and/or ERK inhibitors; and patients who received direct RAS inhibitors.
Statistical analysis was performed using IBM SPSS Statistics version 24 and R version 4.3.1. Multivariate logistic regression models were used to determine the effect of each covariate, including the impact of BRAF alterations on response outcomes. The distributions of overall survival (OS) duration, progression-free survival (PFS) duration, and time to treatment failure (TTF) were estimated by the Kaplan-Meier method. A p-value of less than 0.05 was considered significant. Supplemental Methods, available online, include additional details on statistical analysis.
RESULTS
We included 236 patients (115 male and 121 female) who started treatment on investigational RAF, MEK, and/or ERK inhibitors between April 2016 and November 2023. The majority of patients (81.4%, n = 192) were White or Caucasian and had RAS wild-type status (59.3%, n = 140). All patients received RAF, MEK, and/or ERK inhibitors and no direct RAS inhibitors regardless of RAS status. The most frequent diagnoses were melanoma (20.3%, n = 48) and colorectal cancer (18.6%, n = 44; Table 1).
Table 1.
Characteristics of included patients treated with RAF, MEK, or ERK inhibitors
| Variables | RAS-Mutated# (n = 96) | RAS Wild-Type (n = 140) | Total (N = 236) |
|---|---|---|---|
| Sex | |||
| Female | 53 (55.2%) | 68 (48.6%) | 121 (51.3%) |
| Male | 43 (44.8%) | 72 (51.4%) | 115 (48.7%) |
| Race | |||
| White or Caucasian | 79 (82.3%) | 113 (80.7%) | 192 (81.4%) |
| Asian | 5 (5.2%) | 6 (4.3%) | 11 (4.7%) |
| Black or African American | 7 (7.3%) | 4 (2.9%) | 11 (4.7%) |
| Other or unknown | 5 (5.2%) | 17 (12.1%) | 22 (9.3%) |
| Ethnicity | |||
| Hispanic or Latino | 11 (11.5%) | 24 (17.1%) | 35 (14.8%) |
| Non-Hispanic or Latino | 84 (87.5%) | 115 (82.1%) | 199 (84.3%) |
| Unknown | 1 (1.0%) | 1 (0.7%) | 2 (0.8%) |
| Disease | |||
| Melanoma | 17 (17.7%) | 31 (22.1%) | 48 (20.3%) |
| Colorectal cancer | 27 (28.1%) | 17 (12.1%) | 44 (18.6%) |
| Gynecological cancersa | 16 (16.7%) | 9 (6.4%) | 25 (10.6%) |
| Thyroid cancer | 4 (4.2%) | 19 (13.6%) | 23 (9.7%) |
| Biliary tract cancer | 4 (4.2%) | 15 (10.7%) | 19 (8.1%) |
| Pancreatic cancer | 12 (12.5%) | 6 (4.3%) | 18 (7.6%) |
| Primary CNS tumorsb | 2 (2.1%) | 16 (11.4%) | 18 (7.6%) |
| Non-small cell lung cancer | 4 (4.2%) | 4 (2.9%) | 8 (3.4%) |
| Head and neck cancers | 2 (2.1%) | 4 (2.9%) | 6 (2.5%) |
| Other cancers | 8 (8.3%) | 19 (13.6%) | 27 (11.4%) |
| BRAF mutationsc | |||
| Yes | 8 (8.3%) | 108 (77.1%) | 116 (49.2%) |
| V600 | 5 (5.2%) | 90 (46.3%) | 116 (49.2%) |
| Non-V600 | 3 (3.1%) | 18 (12.9%) | 116 (49.2%) |
| No | 88 (91.7%) | 32 (22.9%) | 120 (50.8%) |
| Combination therapy | |||
| Yes | 45 (46.9%) | 71 (50.7%) | 116 (49.2%) |
| No | 51 (53.1%) | 69 (49.3%) | 120 (50.8%) |
Including KRAS G12A/C/D/R/S/V, KRAS G13D, KRAS Q61L/H/R, KRAS amplifications, NRAS G12A/C/D/S/R, NRAS Q61K/R/L, HRAS G12S, and HRAS Q61R/L.
Including ovarian, endometrial, and cervical cancers.
Including glioblastoma multiforme, pleomorphic xanthoastrocytoma, anaplastic astrocytoma, ganglioglioma, spinal cord astrocytoma, ependymoma, pilocytic astrocytoma, and oligodendroglioma.
Including only pathogenic BRAF mutation.
CNS: central nervous system; ERK: extracellular signal-regulated kinase; MEK: mitogen-activated protein kinase kinase; RAS: rat sarcoma.
Patients without mutations in the RAS family of genes (KRAS, NRAS, and HRAS) had higher response rates than did those with mutations (19.3% vs 4.2%, p = 0.001; Table 2). Similarly, the disease control rate (partial response or stable disease) was higher in patients with RAS-wild-type than in those with RAS mutations (69.3% vs 50.0%, p = 0.003; Table 2). Compared with patients with RAS-wild-type and BRAF-mutated, patients with RAS-mutated and BRAF-wild-type had significantly lower odds of achieving an objective response rate (odds ratio = 0.19 [95% CI, 0.037–0.827], p = 0.03).
Table 2.
Clinical outcomes after RAF, MEK, or ERK inhibitor treatment according to RAS status
| Outcome | RAS-Mutated (n = 96) | RAS-Wild-Type (n = 140) |
|---|---|---|
| PR, n (%) | 4 (4.2) | 27 (19.3) |
| SD, n (%) | 44 (45.8) | 70 (50.0) |
| PD, n (%) | 48 (50.0) | 43 (30.7) |
| PFS, median (weeks) | 9 (95% CI, 7–11) | 17 (95% CI, 13–21) |
| TTF, median (weeks) | 10 (95% CI, 8–12) | 19 (95% CI, 15–23) |
| OS, median (weeks) | 39 (95% CI, 28–50) | 60 (95% CI, 45–75) |
ERK: extracellular signal-regulated kinase; MEK: mitogen-activated protein kinase kinase; OS, overall survival; PD: progressive disease; PFS: progression-free survival; PR: partial response; SD: stable disease; RAS: rat sarcoma; RAF: rapidly accelerated fibrosarcoma; TTF: time to treatment failure.
The PFS duration was significantly longer in patients without RAS mutations than in those with mutations (median, 17 weeks vs 9 weeks, p < 0.001; Supplemental Figure 1). Similarly, the median TTF and OS were significantly longer in patients without RAS mutations than in those with mutations (median TTF duration, 19 weeks vs 10 weeks, p < 0.001; median OS duration, 60 weeks vs 39 weeks, p = 0.005; Supplemental Figure 1).
DISCUSSION
Herein, we demonstrate that in a pan-cancer trial cohort, mutations in the RAS family of genes were associated with worse clinical outcomes after treatment with investigational agents inhibiting downstream RAF, MEK, and/or ERK. This underscores the critical role of RAS mutational status as a key determinant of response to MAPK pathway–targeted agents. The significant difference in the objective response rate between RAS wild-type (18.1%) and RAS-mutated (2.2%) patients highlights the potential of RAS alterations to confer inherent resistance to RAF, MEK, and ERK inhibitors. This finding aligns with those of previous studies suggesting an interplay between RAS and RAF, MEK, and ERK.[4–9] Even in clinical studies that show that RAF, MEK, and ERK inhibitors have some benefit in patients with RAS-altered cancers, the response rates were relatively low and mainly observed in specific variants. For example, the NEMO trial (NCT01763164) showed better clinical outcomes with binimetinib than with dacarbazine in patients with melanoma harboring NRAS Q61x mutations. However, the overall response rate in the binimetinib arm was relatively low (15%), which aligned with our data.[11] The underlying mechanism of this differential response is likely multifaceted. Beyond the constitutive activation of the MAPK pathway in RAS-mutated tumors, other factors, such as compensatory signaling pathways and the tumor microenvironment, may also contribute to resistance to RAF, MEK, and ERK inhibitors. Further research is needed to fully elucidate the molecular underpinnings of this phenomenon and to identify strategies to overcome resistance in RAS-mutated tumors. Of note, other studies have shown possible responses to RAF, MEK, and ERK inhibitors in tumors harboring specific RAS variants.[12–14]
Our study has several limitations. First, this was a retrospective study of a patient population that was treated as part of phase 1 clinical trials, which limits the generalizability of the results. The analyzed cohort included a heterogeneous group of patients with varying disease types and therapeutic regimens with differing activity and approval trajectory. Responses to monotherapy may have also differed from responses to combination therapy, and outcomes of patients treated in dose escalation would be different from outcomes of patients treated in dose expansion. In addition, different disease biologies have historically shown distinct responses to RAF, MEK, and ERK inhibition. For example, responses have been limited in patients with colorectal cancer because of EGFR activation.[15] Prior therapy with MAPK inhibitors was not included in the analysis and could have affected the results. The ability of different agents to penetrate the central nervous system can affect clinical responses in primary central nervous system tumors. In addition, the sensitizing impact of other MAPK pathway alterations could have affected the results, although a multivariate analysis suggested that RAS alterations have an independent predictive effect. RAS mutations differ from one another; thus, the small number of specific mutations included in this study limited further analysis of mutation-specific differences. Finally, the predictive value of RAS alterations should be interpreted with caution in the context of the known prognostically worse outcomes in those cohorts.
CONCLUSIONS
This study suggests that RAF, MEK, and ERK inhibition may have limited clinical activity in patients with RAS mutations, which reinforces the importance of RAS mutational status as a predictive biomarker for response. Further exploration is needed in larger studies with more homogeneous populations, while controlling for potential confounding factors.
Supplementary Material
Acknowledgments
The authors would like to thank Ann Sutton at the MD Anderson Research Medical Library Editing Services for assistance in language editing. This research was supported in part by the NCI Cancer Center Support (Grant P30CA016672) and Clinical and Translational Science Award (Grant 1UM1 TR0045906) to The University of Texas MD Anderson Cancer Center.
Conflicts of Interest
Mohamed A. Gouda reports participation in advisory board for Immunocore, Caris Life Sciences, and Foundation Medicine. Siqing Fu received clinical trial research support and grant funding through the institution from NIH/NCI P30CA016672—Core Grant (CCSG Shared Resources); Abbisko, Antengene, BeiGene, BeyongSpring Pharmaceuticals, Inc., BioAtla, LLC, Boehringer Ingelheim, CUE Biopharma, Inc., DEKA Biosciences, Eli Lilly & Co., Exelixis, Greenfire Bio, Inc., Hookipa Biotech, IMV, Inc., Innovent Biologics, Co., Ltd., Jazz Pharmaceuticlals, K-Group Beta, Lantern Pharma Inc., Lyvgen Biopharm, Co., Ltd., MacroGenics, MediLink Therapeutics, Co. Ltd., Millennium Pharmaceuticals, Inc., Nerviano Medical Sciences, NeuPharma, Inc., NextCure, Inc., Ningbo NewBay Technology Development Co., Ltd., Novartis, NovoCure, Nykode Therapeutics AS., Parexel International, LLC, PharmaMar USA, Inc., Pionyr Immunotherapeutics, Inc., PureTech Health, LLC, Qurgen, Inc., Shanghai Huaota Biopharmaceutical Co., Ltd., Sellas Life Sciences Group, Soricimed Biopharma, Inc., SQZ Biotechnologies, Sumitomo Dainippon, Taiho Oncology and NCCN, Treadwell Therapeutics, Turnstone Biologics, Tyligand Bioscience, Ltd., Virogin Biotech, Ltd. Daniel D. Karp reported NIH Grants Clinical Translational Science Award 2019–2024, NCI Core Grant, Clinical Translational 2002–2023, Myriad Drug Companies. Consulting—Black Beret Life Sciences, Affigen Advisory Board, hosplatin Advisory Board, Research Support, Travel Support as allowed. Aung Naing reports research funding from NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor/Millendo, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol-Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Eli Lilly, Kymab, PsiOxus, Arcus Biosciences, NeoImmuneTech, Immune-Onc Therapeutics, Surface Oncology, Monopteros Therapeutics, BioNTech SE, Seven & Eight Biopharma, and SOTIO Biotech AG; being on advisory boards of and receiving consulting fees from CTI, Deka Biosciences, Janssen Biotech, NGM Bio, PsiOxus Therapeutics, Immune-Onc Therapeutics, STCube Pharmaceuticals, OncoSec KEYNOTE-695, Genome & Company, CytomX Therapeutics, Nouscom, Merck Sharp & Dohme Corp, Servier, Lynx Health, AbbVie, PsiOxus; travel and accommodation expense from ARMO BioSciences, NeoImmuneTech, NGM Biopharmaceuticals; and honoraria for speaking engagements from AKH Inc., The Lynx Group, Society for Immunotherapy of Cancer (SITC), Korean Society of Medical Oncology (KSMO), Scripps Cancer Care Symposium, ASCO Direct Oncology Highlights, European Society for Medical Oncology (ESMO), CME Outfitters. Sarina A. Piha-Paul reports clinical trial research support and grant funding through the institution from AbbVie, Inc., ABM Therapeutics, Inc., Acepodia, Inc, Alkermes, Aminex Therapeutics, BioMarin Pharmaceutical, Inc, Boehringer Ingelheim, Bristol Myers Squib, Cerulean Pharma, Inc., Chugai Pharmaceutical Co., Ltd, Curis, Inc., Cyclacel Pharmaceuticals, Daiichi Sankyo, Eli Lilly, ENB Therapeutics, Epigenetix Inc., Five Prime Therapeutics, F-Star Beta Limited, F-Star Therapeutics, Gene Quantum, Genmab A/S, Gilead Sciences, Inc., GlaxoSmithKline, Helix BioPharma Corp., Hengrui Pharmaceuticals, Co., Ltd., HiberCell, Inc., Immunomedics, Inc., Incyte Corp., Jacobio Pharmaceuticals Co., Ltd., Jiangsu Simcere Pharmaceutical Co., Ltd., Loxo Oncology, Inc., Lytix Biopharma AS, Medimmune, LLC, Medivation, Inc., Merck Sharp and Dohme Corp., Nectin Therapeutics, Ltd., Novartis Pharmaceuticals, Nurix, Pieris Pharmaceuticals, Inc., Pfizer, Phanes Therapeutics, Principia Biopharma, Inc., Puma Biotechnology, Inc., Purinomia Biotech, Inc., Rapt Therapeutics, Inc., Replimune; Roche/Blueprint, Seattle Genetics, Silverback Therapeutics, Shasqi, Inc., Synlogic Therapeutics, Taiho Oncology, Tesaro, Inc., Theradex Oncology, Toragen Therapeutics, Inc., TransThera Bio, Xencor, Inc, ZielBio, Inc., NCI/NIH, P30CA016672—Core Grant (CCSG Shared Resources); and working as a consultant for CRC Oncology. Jordi Rodon reports non-financial support and reasonable reimbursement for travel from European Society for Medical Oncology and Loxo Oncology; receiving consulting and travel fees from Ellipses Pharma, Molecular Partners, IONCTURA, Sardona, Mekanistic, Amgen, Merus, MonteRosa, Aadi and Bridgebio (including serving on the scientific advisory board); consulting fees from Vall d’Hebron Institute of Oncology/Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, Boxer Capital, LLC, Tang Advisors, LLC and Guidepoint; receiving research funding from Blueprint Medicines, Merck Sharp & Dohme, Hummingbird, AstraZeneca, Yingli, Vall d’Hebron Institute of Oncology/Cancer Core Europe; and serving as investigator in clinical trials with Cancer Core Europe, Symphogen, BioAlta, Pfizer, Kelun-Biotech, GlaxoSmithKline, Taiho, Roche Pharmaceuticals, Hummingbird, Yingli, Bicycle Therapeutics, Merus, AadiBioscience, ForeBio, Loxo Oncology, Hutchinson MediPharma, Ideaya, Amgen, Tango Therapeutics, Mirati, Linnaeus Therapeutics, MonteRosa, Kinnate, Yingli, Debio, BioTheryX, Storm Therapeutics, Beigene, MapKure, Relay, Novartis, FusionPharma, C4 Therapeutics, Scorpion Therapeutics, Incyte, Fog Pharmaceuticals, Tyra, Nuvectis Pharma. Timothy A. Yap reported consulting for: AbbVie, Acrivon, Adagene, Almac, Aduro, Amgen Inc., Amphista, Artios, Astex, AstraZeneca, Athena, Atrin, Avenzo, Avoro, Axiom, Baptist Health Systems, Bayer, Beigene, BioCity Pharma, Blueprint, Boxer, BridGene Biosciences, Bristol Myers Squibb, C4 Therapeutics, Calithera, Cancer Research UK, Carrick Therapeutics, Circle Pharma, Clovis, Cybrexa, Daiichi Sankyo, Dark Blue Therapeutics, Debiopharm, Diffusion, Duke Street Bio, 858 Therapeutics, EcoR1 Capital, Ellipses Pharma, EMD Serono, Entos, FoRx Therapeutics AG, F-Star, Genesis Therapeutics, Genmab, Glenmark, GLG, Globe Life Sciences, Grey Wolf Therapeutics, GSK, Guidepoint, Ideaya Biosciences, Idience, Ignyta, I-Mab, ImmuneSensor, Impact Therapeutics, Institut Gustave Roussy, Intellisphere, Jansen, Joint Scientific Committee for phase I trials in Hong Kong, Kyn, Kyowa Kirin, MEI pharma, Mereo, Merck, Merit, Monte Rosa Therapeutics, Natera, Nested Therapeutics, Nexys, Nimbus, Novocure, Odyssey Therapeutics, OHSU, OncoSec, Ono Pharma, Onxeo, PanAngium Therapeutics, Pegascy, PER, Pfizer, Piper-Sandler, Pliant Therapeutics, Prelude Therapeutics, Prolynx, Protai Bio, Radiopharma Theranostics, Repare, resTORbio, Roche, Ryvu Therapeutics, SAKK, Sanofi, Schrodinger, Servier, Synnovation, Synthis Therapeutics, Tango, TCG Crossover, TD2, Terremoto Biosciences, Tessellate Bio, Theragnostics, Terns Pharmaceuticals, Thryv Therapeutics, Tolremo, Tome, Trevarx Biomedical, Varian, Veeva, Versant, Vibliome, Voronoi Inc, Xinthera, Zai Labs and ZielBio; grant and research support from: Artios, AstraZeneca, Bayer, Beigene, BioNTech, Blueprint, BMS, Boundless Bio, Clovis, Constellation, CPRIT, Cyteir, Department of Defense, Eli Lilly, EMD Serono, Exelixis, Forbius, F-Star, GlaxoSmithKline, Genentech, Gilead, Golfers against Cancer, Haihe, Ideaya, ImmuneSensor, Insilico Medicine, Ionis, Ipsen, Jounce, Karyopharm, KSQ, Kyowa, Merck, Mirati, Novartis, NIH/NCI, Pfizer, Pliant, Prelude, Ribon Therapeutics, Regeneron, Repare, Roche, Rubius, Sanofi, Scholar Rock, Seattle Genetics, Synnovation, Tango, Tesaro, V Foundation, Vivace, Zenith and Zentalis; and stockholder in Seagen. Funda Meric-Bernstam reported consulting for AstraZeneca Pharmaceuticals, Becton Dickinson, Calibr (a division of Scripps Research), Daiichi Sankyo, Dava Oncology, Debiopharm, EcoR1 Capital, eFFECTOR Therapeutics, Elevation Oncology, Exelixis, GT Aperion, Incyte, Jazz Pharmaceuticals, LegoChem Biosciences, Lengo Therapeutics, Menarini Group, Molecular Templates, Protai Bio, Ribometrix, Roche, Tallac Therapeutics, Tempus, Zymeworks; advisory committee for Biovica, Cybrexa, FogPharma, Guardant Health, Harbinger Health, Karyopharm Therapeutics, LOXO-Oncology, Mersana Therapeutics, OnCusp Therapeutics, Sanofi Pharmaceuticals, Seagen, Theratechnologies, Zentalis Pharmaceuticals; sponsored research (to the institution) from Jazz Pharmaceuticals, Zymeworks, Aileron Therapeutics, Inc., AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., Debiopharm International, eFFECTOR Therapeutics, Genentech Inc., Guardant Health Inc., Klus Pharma, Takeda Pharmaceutical, Novartis, Puma Biotechnology Inc., Taiho Pharmaceutical Co.; honoraria from Dava Oncology; and other (travel related) from European Organization for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO), Cholangiocarcinoma Foundation, Dava Oncology. David S. Hong reported Research(Inst)/Grant Funding (Inst): AbbVie, Adaptimmune, Adlai-Nortye, Amgen, Astelles, AstraZeneca, Bayer, Biomea, Bristol-Myers Squibb, Daiichi-Sankyo, Deciphera, Eisai, Eli Lilly, Endeavor, Erasca, F. Hoffmann-LaRoche, Fate Therapeutics, Genentech, Genmab, Immunogenesis, Infinity, Kyowa Kirin, Merck, Mirati, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, Revolution Medicine, SeaGen, STCube, Takeda, TCR2, Turning Point Therapeutics, VM Oncology; travel, accommodations, expenses: AACR, ASCO, CLCC, Bayer, Genmab, SITC, Telperian; consulting, speaker, or advisory role: 28Bio, Abbvie, Acuta, Adaptimmune, Alkermes, Alpha Insights, Amgen, Affini-T, Astellas, Aumbiosciences, Axiom, Baxter, Bayer, Boxer Capital, BridgeBio, CARSgen, CLCC, COG, COR2ed, Cowen, Ecor1, EDDC, Erasca, Exelixis, Fate Therapeutics, F. Hoffmann-La Roche, Genentech, Gennao Bio, Gilead, GLG, Group H, Guidepoint, HCW Precision Oncology, Immunogenesis, Incyte Inc, Inhibrix Inc, InduPro, Janssen, Jounce Therapeutics Inc, Lan-Bio, Liberium, MedaCorp, Medscape, Novartis, Numab, Oncologia Brasil, ORI Capital, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, Projects in Knowledge, Quanta, RAIN, Ridgeline, Revolution Medicine SeaGen, Stanford, STCube, Takeda, Tavistock, Trieza Therapeutics, T-Knife, Turning Point Therapeutics, WebMD, YingLing Pharma, Ziopharm; and other ownership interests: Molecular Match (Advisor), OncoResponse (Founder, Advisor), Telperian (Founder, Advisor).
Supplemental Material
Supplemental materials are available online with the article.
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