About

Nicole Miller is an artist working mainly with video, living and working in Southern California. Her work stems from the possibility that representation allows for reconstitution. Using video installation and sculpture, Miller proposes that active viewing can be used as a tool to reconstitute personal histories, or even one's own body. She has had solo exhibitions in several institutions including SFMOMA, Marfa Ballroom, Centre D'art Contemporain Geneva, Kunst Werk Berlin, the California African American Museum, Tucson Museum of Contemporary Art, The Highline NYC, and The LA County Museum in Los Angeles. Miller's work has been included in many group shows and Biennials at venues such as The Studio Museum in Harlem, The LA Biennial at the Hammer Museum, Musée d'art contemporain de Lyon, and The San Francisco Museum of Art. She was a prize winner of the Rome prize at the American Academy Rome and has received awards including a Guggenheim, The William H Johnson Prize, the Rema Hort Mann prize, Louis Comfort Tiffany prize, and the Artadia Los Angeles award. Her work is part of the collections at the LA County Museum, the Hammer Museum, and SFMOMA, among others.

Research topics

• Biology
• Cancer research
• Cell biology
• Genetics
• Biochemistry
• Pharmacology
• Chemistry
• Medicine
• Internal medicine
• Computational biology
• Bioinformatics

Selected publications

• Pan-RAF inhibitor exarafenib targets BRAF class II/III NSCLC and reveals ARAF-KSR1 resistance and combination strategies

  Nature Communications · 2026-02-07 · 1 citations

  articleOpen access

  Oncogenic BRAF mutations, including those in non-small cell lung cancer (NSCLC), are classified as Class I, II, or III. While approved therapies exist for BRAF Class I mutants, no approved therapies exist for Class II and III BRAF-mutated NSCLC. Analysis of a circulating tumor DNA database reveals Class II and III mutations comprise ~65% of BRAF-mutant NSCLC cases, with Class II patients showing worse outcomes than Class I. Exarafenib, a distinct pan-RAF inhibitor, demonstrates potent activity against BRAF Class II and III mutant preclinical models and initial clinical activity. Resistance studies reveal rewiring to an ARAF-mediated bypass pathway, characterized by RAS-mediated ARAF-KSR1 complexes maintaining MAPK signaling despite pan-RAF inhibitor treatment. RAS or MEK inhibition co-targeting is effective against this resistance mechanism. This study provides preclinical rationale for clinical testing of exarafenib in BRAF Class II/III cancers and unveils RAS-mediated ARAF-KSR1 complex formation as a resistance mechanism and rational co-therapy strategies.

  PublisherDOI

• OA03.01 Unveiling the Anti-Tumor Activity of Exarafenib in BRAF-Mutated NSCLC Through Genomic Analysis and Combined Preclinical, Clinical Outcomes

  Journal of Thoracic Oncology · 2025-04-01

  article
  PublisherDOI

• Targeting BRAF Class II and III Mutations in NSCLC with the pan-RAF inhibitor Exarafenib Reveals ARAF-KSR1-Mediated Resistance and Rational Combination Strategies

  Research Square · 2025-10-09

  preprintOpen access
  PublisherOA PDFDOI

• CDK4 selective inhibition improves preclinical anti-tumor efficacy and safety

  Cancer Cell · 2025-03-01 · 49 citations

  articleOpen access

  CDK4/6 inhibitors have revolutionized treatment of hormone receptor positive (HR+), HER2 non-amplified (HER2-) breast cancer. Yet, all "dual" CDK4/6 inhibitors show common dose-limiting hematologic toxicities, foremost neutropenia. This poses challenges to provide these agents at concentrations necessary to extinguish cell cycling in tumors. HR+ breast cancer cells are highly dependent on CDK4 but not CDK6. By contrast, CDK4 is dispensable for human bone marrow derived cells, due to the primary and compensatory role of CDK6 in hematopoiesis. This prompted us to develop atirmociclib (PF-07220060), a next-generation CDK4 selective inhibitor. Atirmociclib's impact on circulating neutrophils was reduced, in proportion with its increase in CDK4 versus CDK6 selectivity. Realized dose intensification led to greater CDK4 inhibition and deeper anti-tumor responses, pointing to CDK4 target coverage as a limiting factor of CDK4/6 inhibitor efficacy. We also highlight combinatorial agents that may counter acquired resistance to CDK4 selective inhibition and widen its clinical application.

  PublisherOA PDFDOI

• Abstract 6389: Unveiling the potent anti-tumor activity and underlying mechanism of action of the novel pan-RAF inhibitor exarafenib in BRAF-mutated NSCLC

  Cancer Research · 2025-04-21

  article

  Abstract Somatic BRAF alterations occur in up to 5% of non-small cell lung cancer (NSCLC) cases and comprise three mechanistically distinct molecular subtypes: Class I alterations (e.g., V600E) function as constitutively active monomers, Class II alterations that signal as RAS-independent mutant BRAF homodimers, and Class III alterations that activate MAPK signaling via RAS-dependent mutant BRAF/wild-type RAF heterodimers. While BRAF V600E (Class I) mutations are effectively targeted by approved therapies that are active against these oncogenic BRAF monomers, there are no established targeted treatments for both Class II and III BRAF mutations that operate as BRAF dimers in NSCLC. Analysis of the GuardantINFORM™ database revealed that these untreatable Class II and III BRAF mutations comprise 65% of BRAF-mutant NSCLC cases, with Class II mutations associated with significantly worse survival compared to Class I (median survival 514 vs 818 days, HR: 1.4, P=0.0395). Here we evaluate exarafenib, a novel type 2 pan-RAF inhibitor designed to target both monomeric and dimeric forms of RAF proteins by binding the αC-helix-IN and DFG-out conformations. Through comprehensive mechanistic studies, we demonstrate that while exarafenib induces RAF dimerization, it maintains potent inhibition of both monomeric and dimeric RAF proteins with high selectivity for RAF kinases, leading to effective suppression of downstream MAPK pathway signaling. In preclinical studies, exarafenib showed robust anti-tumor activity in BRAF-mutant NSCLC cell lines and patient-derived xenograft models, with favorable pharmacokinetic and pharmacodynamic properties. Clinical case studies revealed promising responses, including a partial response and sustained disease control for over two years in a patient with BRAF G469S mutation, and a significant initial response lasting approximately 32 weeks in a patient with TMEM106B-BRAF fusion. Through analysis of acquired resistance models, we identified RAS activation as a key resistance mechanism and biomarker that was accompanied by sustained MAPK pathway signaling. Based on this mechanism, we evaluated combination strategies and found that co-targeting MEK with binimetinib provided synergistic anti-tumor effects both in vitro and in vivo, while maintaining tolerability. These mechanistic insights provide strong biological rationale for the ongoing Phase 1 trial (KN-8701; NCT04913285) evaluating exarafenib as monotherapy and in combination with binimetinib in BRAF-altered solid tumors including NSCLC and NRAS-mutant melanoma, offering a potential therapeutic strategy for patients that currently lack effective targeted treatment options. Citation Format: Tadashi Manabe, Tim Sen Wang, Paul Severson, Nichol Miller, Catherine Lee, Elifnur Yay Donderici, Nicole Zhang, Yu-ting Chou, Daniel L. Kerr, Wei Wu, Kathryn B. Grandinetti, Liliana Soroceanu, Robert J. Pelham, Eric S. Martin, Eric A. Murphy, Vishesh Khanna, Joel W. Neal, Christopher T. Chen, Shumei Kato, Richard Williams, Trever Bivona. Unveiling the potent anti-tumor activity and underlying mechanism of action of the novel pan-RAF inhibitor exarafenib in BRAF-mutated NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6389.

  PublisherDOI

• Discovery of Highly Selective Inhibitors of Microtubule-Associated Serine/Threonine Kinase-like (MASTL)

  Journal of Medicinal Chemistry · 2024-11-05 · 5 citations

  article

  By virtue of its role in cellular proliferation, microtubule-associated serine/threonine kinase-like (MASTL) represents a novel target and a first-in-class (FIC) opportunity to provide a new impactful therapeutic agent to oncology patients. Herein, we describe a hit-to-lead optimization effort that resulted in the delivery of two highly selective MASTL inhibitors. Key strategies leveraged to enable this work included structure-based drug design (SBDD), analysis of lipophilic efficiency (LipE) and novel synthesis. The resulting advanced lead compounds enabled a tumor growth inhibition study which was pivotal in assessing the potential value of MASTL as an oncology therapeutic target.

  PublisherDOI

• Discovery of PF-07265028, A Selective Small Molecule Inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) for the Treatment of Cancer

  Journal of Medicinal Chemistry · 2024-12-09 · 17 citations

  article

  Hematopoietic progenitor kinase 1 (HPK1/MAP4K1) represents a high interest target for the treatment of cancer through an immune-mediated mechanism. Herein we present highlights of the drug discovery campaign within the lactam/azalactam series of inhibitors that yielded a small molecule (21, PF-07265028), which was advanced to a phase 1 clinical trial (NCT05233436). Key components of the discovery effort included optimization of potency through mitigation of ligand strain as guided by the use of cocrystal structures, mitigation of ADME liabilities (plasma instability and fraction metabolism by CYP2D6), and optimization of kinase selectivity, particularly over immune-modulating kinases with high homology to HPK1. Structure-based drug design via leveraging cocrystal structures and lipophilic efficiency analysis proved to be valuable tools that ultimately enabled the delivery of a clinical-quality small molecule inhibitor of HPK1.

  PublisherDOI

• Discovery of KIN-3248, An Irreversible, Next Generation FGFR Inhibitor for the Treatment of Advanced Tumors Harboring FGFR2 and/or FGFR3 Gene Alterations

  Journal of Medicinal Chemistry · 2024 · 16 citations

  • Cancer research
  • Biology
  • Genetics

  is currently in phase I clinical development for the treatment of advanced tumors harboring FGFR2 and/or FGFR3 gene alterations.

  PublisherOA PDFDOI

• The Discovery of Exarafenib (KIN-2787): Overcoming the Challenges of Pan-RAF Kinase Inhibition

  Journal of Medicinal Chemistry · 2024-01-17 · 13 citations

  articleOpen access

  RAF, a core signaling component of the MAPK kinase cascade, is often mutated in various cancers, including melanoma, lung, and colorectal cancers. The approved inhibitors were focused on targeting the BRAFV600E mutation that results in constitutive activation of kinase signaling through the monomeric protein (Class I). However, these inhibitors also paradoxically activate kinase signaling of RAF dimers, resulting in increased MAPK signaling in normal tissues. Recently, significant attention has turned to targeting RAF alterations that activate dimeric signaling (class II and III BRAF and NRAS). However, the discovery of a potent and selective inhibitor with biopharmaceutical properties suitable to sustain robust target inhibition in the clinical setting has proven challenging. Herein, we report the discovery of exarafenib (15), a highly potent and selective inhibitor that intercepts the RAF protein in the dimer compatible αC-helix-IN conformation and demonstrates anti-tumor efficacy in preclinical models with BRAF class I, II, and III and NRAS alterations.

  PublisherOA PDFDOI

• Supplementary Methods from FAK Inhibition Disrupts a β5 Integrin Signaling Axis Controlling Anchorage-Independent Ovarian Carcinoma Growth

  2023-04-03

  preprintOpen access

  <p>PDF file - 59K</p>

  PublisherOA PDFDOI

Recent grants

• Role of p190RhoGEF (Rgnef) in cell motility and tumor progression

  NIH · $154k · 2011–2014

Frequent coauthors

• David D. Schlaepfer

  54 shared

• Xiao Lei Chen

  Moores Cancer Center

  43 shared

• Isabelle Tancioni

  Moores Cancer Center

  38 shared

• Sean Uryu

  Moores Cancer Center

  37 shared

• Christine Lawson

  37 shared

• Christine Jean

  Centre de Recherche en Cancérologie de Toulouse

  31 shared

• Kristy Ward

  27 shared

• Nina R. Shah

  Colorado Permanente Medical Group

  24 shared

Labs

• Nicole MillerPI

Awards & honors

• Rome prize at the American Academy Rome
• Guggenheim
• The William H Johnson Prize
• Rema Hort Mann prize
• Louis Comfort Tiffany prize