About

Swarnali Acharyya, PhD, is an Associate Professor of Pathology and Cell Biology at Columbia University Irving Medical Center, within the Institute for Cancer Genetics. Her laboratory focuses on studying metastasis, which is the predominant cause of cancer-patient mortality. Her research investigates what makes metastasis lethal and how to target metastases to improve patient outcomes. The lab studies metastasis as a systemic disease involving crosstalk between metastatic cancer cells and both cancer-inhabiting and cancer-free organs of the body. Key areas of her research include therapy resistance of metastatic tumors and the systemic effects of metastatic disease, such as cachexia. Her work has identified mechanisms promoting therapy resistance, including a novel S100A9-ALDH1A1-retinoic acid signaling axis that promotes resistance in brain metastases from EGFR-mutant lung cancer patients. She also studies the metabolic deregulation of organs affected by metastasis, particularly focusing on cachexia, a condition characterized by loss of skeletal muscle mass and function. Her research has identified ZIP14 as a marker and mediator of cachexia, demonstrating that muscle tissue can detect early metastatic relapse. Her work aims to inform the development of more effective and durable treatments for metastatic cancer patients to prolong survival.

Research topics

• Cancer research
• Immunology
• Biology
• Internal medicine
• Medicine
• Bioinformatics

Selected publications

• A new, immunocompetent brain-metastatic mouse model of HER2-positive breast cancer

  Clinical & Experimental Metastasis · 2025-04-12

  articleSenior author
  PublisherDOI

• Central Nervous System Metastases from Primary Lung Carcinoma: Significance of RNA Fusion Testing and Early Versus Late Metastases

  Journal of Personalized Medicine · 2025-05-01

  articleOpen access

  Background/Objectives: While the genomic landscape of primary lung carcinomas is well characterized, there is a relative scarcity of fusion data on corresponding central nervous system (CNS) metastases. This study aimed to elucidate the molecular profiles of CNS metastases to (1) assess the significance of a combined DNA–reflex RNA fusion testing approach and (2) compare the mutational landscape between patients who present initially [early (≤2 months)] with CNS metastases and those who develop CNS metastases thereafter [late (>2 months)]. Methods: We performed a retrospective search of CNS metastases of adenocarcinoma of probable lung origin interrogated by targeted DNA–reflex RNA next-generation sequencing (NGS). The DNA NGS panel included the driver mutations EGFR, BRAF, KRAS, MET, and ERBB2. RNA NGS included ALK, RET, ROS1, and MET. Additionally, mutational profiles were examined between those with early versus late CNS metastases. Results: Of the 58 patients, 44 (75.9%) had mutations or alterations, including 34 identified by DNA NGS [EGFR (n = 17; 50.0%), KRAS (n = 15; 44.1%), MET (n = 2; 5.9%)] and 10/24 by RNA NGS [ALK (n = 7; 70%), MET (n = 2; 20%), ROS1 (n = 1; 10%)]. Of all patients, 32 (55%) presented with early and 26 (45%) with late CNS metastases. Although patients with early metastases had worse survival compared to those with late metastases (p < 0.001), there were no statistically significant differences in the mutational profiles between the two cohorts. Conclusions: A significant proportion of CNS metastases without driver mutations identified by DNA NGS had targetable alterations identified by RNA NGS (10/24, 41.7%). In summary, a combined DNA with reflex RNA fusion testing approach plays a significant role in detecting and potentially managing CNS metastases. Comprehensive prospective studies are essential to elucidate the differences between early and late CNS metastases.

  PublisherOA PDFDOI

• BSBM-12 TARGETING OSIMERTINIB-RESISTANT BRAIN METASTASIS USING RAR ANTAGONISTS

  Neuro-Oncology Advances · 2024-08-01

  articleOpen accessSenior author

  Abstract It is estimated that one-third of EGFR-mutant lung cancer patients develop brain metastasis during the course of their disease. Brain metastasis is associated with a significant decline in cognitive and motor function, daily functioning, and accelerated mortality. Brain metastasis is a severe complication for 45% of patients with EGFR-mutant lung cancer that drastically reduces their quality of life and survival. Fortunately, EGFR-tyrosine kinase inhibitors (TKIs) such as osimertinib showed excellent blood-brain-barrier permeability and resulted in dramatic responses in patients with brain metastases. However, despite a striking initial response, osimertinib-treated patients eventually develop relapse, often to the brain, and succumb to death. With this fatal malignancy, it is important to understand underlying mechanisms of brain metastasis to improve treatment outcomes, which is an unmet need in the field. To study mechanisms of brain relapse, we generated osimertinib treatment-response-and-relapse mouse models using human lung cancer cells harboring osimertinib-sensitive EGFR-activating mutations. Using these new brain relapse models of EGFR-mutant lung cancer, we identified that a S100A9-ALDH1A1-RA signaling axis endows cancer cells with the ability to thrive in the brain despite on-target inhibition of EGFR activity by osimertinib. Mechanistically, we show that S100A9 upregulates ALDH1A1 expression and activate the retinoic acid (RA) signaling pathway in cancer cells, which promotes brain relapse. We demonstrate that the genetic repression of S100A9, ALDH1A1, or retinoic acid receptor (RAR) in cancer cells, or treatment with a pan-retinoic-acid-receptor antagonist, dramatically reduces brain metastasis in independent preclinical models of brain relapse. Importantly, S100A9 expression in cancer cells correlates with poor PFS in patients on osimertinib. Based on these preclinical findings, we propose that RAR antagonist treatment can be tested in patients to target osimertinib-resistant brain metastases. Notably, intracellular S100A9 expression in cancer cells can be used as a biomarker to stratify patients who might benefit from this combination treatment.

  PublisherOA PDFDOI

• FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer

  EMBO Molecular Medicine · 2024-07-02 · 7 citations

  articleOpen accessSenior author

  Abstract Acquired resistance to PARP inhibitors (PARPi) remains a treatment challenge for BRCA 1/2-mutant breast cancer that drastically shortens patient survival. Although several resistance mechanisms have been identified, none have been successfully targeted in the clinic. Using new PARPi-resistance models of Brca1 - and Bard1 -mutant breast cancer generated in-vivo, we identified FLT1 (VEGFR1) as a driver of resistance. Unlike the known role of VEGF signaling in angiogenesis, we demonstrate a novel, non-canonical role for FLT1 signaling that protects cancer cells from PARPi in-vivo through a combination of cell-intrinsic and cell-extrinsic pathways. We demonstrate that FLT1 blockade suppresses AKT activation, increases tumor infiltration of CD8 + T cells, and causes dramatic regression of PARPi-resistant breast tumors in a T-cell-dependent manner. Moreover, PARPi-resistant tumor cells can be readily re-sensitized to PARPi by targeting Flt1 either genetically ( Flt1 -suppression) or pharmacologically (axitinib). Importantly, a retrospective series of breast cancer patients treated with PARPi demonstrated shorter progression-free survival in cases with FLT1 activation at pre-treatment. Our study therefore identifies FLT1 as a potential therapeutic target in PARPi-resistant, BRCA1/2 -mutant breast cancer.

  PublisherOA PDFDOI

• Weight loss in patients on osimertinib for metastatic <i>EGFR</i>-mutant non-small cell lung cancer

  The Oncologist · 2024-12-19 · 3 citations

  articleOpen access

  BACKGROUND: Cachexia is characterized by weight loss and decline in muscle mass and function and is a poor prognostic factor among patients with cancer. Patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC) derive remarkable survival benefits with osimertinib, a third-generation EGFR tyrosine kinase inhibitor. It is not known whether patients treated with osimertinib experience any weight loss or whether weight loss impacts patient outcomes. Therefore, we sought to describe the frequency and consequences of weight loss in this patient population. MATERIALS AND METHODS: We conducted a single-center retrospective pilot study of 56 patients treated with first-line osimertinib for metastatic EGFR-mutant NSCLC. We defined on-treatment weight loss as a loss of ≥5% body weight at 6 or 12 months of treatment. We described the characteristics of patients with and without on-treatment weight loss and differences in progression-free survival (PFS), time on treatment with osimertinib, and overall survival (OS). RESULTS: Forty-six percent (n = 26) of patients met the criteria for on-treatment weight loss. There were no significant differences in patient or disease characteristics between patients with and without weight loss. Compared to patients without weight loss, patients with weight loss had similar PFS and time on treatment with osimertinib. Yet, patients with weight loss had significantly worse overall survival (HR 4.91, 95% CI, 1.56-15.5, P = .007). CONCLUSION: Weight loss was observed in nearly half of patients with metastatic EGFR-mutant NSCLC treated with osimertinib, and patients with weight loss had significantly worse overall survival.

  PublisherOA PDFDOI

• Data from Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in &lt;i&gt;EGFR&lt;/i&gt;-Mutant Lung Cancer

  2023-04-04

  preprintOpen accessSenior author

  &lt;div&gt;Abstract&lt;p&gt;The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in patients with &lt;i&gt;EGFR&lt;/i&gt;-mutant lung cancer, including those with brain metastases. However, despite striking initial responses, osimertinib-treated patients eventually develop lethal metastatic relapse, often to the brain. Although osimertinib-refractory brain relapse is a major clinical challenge, its underlying mechanisms remain poorly understood. Using metastatic models of &lt;i&gt;EGFR&lt;/i&gt;-mutant lung cancer, we show that cancer cells expressing high intracellular S100A9 escape osimertinib and initiate brain relapses. Mechanistically, S100A9 upregulates ALDH1A1 expression and activates the retinoic acid (RA) signaling pathway in osimertinib-refractory cancer cells. We demonstrate that the genetic repression of S100A9, ALDH1A1, or RA receptors (RAR) in cancer cells, or treatment with a pan-RAR antagonist, dramatically reduces brain metastasis. Importantly, S100A9 expression in cancer cells correlates with poor PFS in osimertinib-treated patients. Our study, therefore, identifies a novel, therapeutically targetable S100A9–ALDH1A1–RA axis that drives brain relapse.&lt;/p&gt;Significance:&lt;p&gt;Treatment with the EGFR TKI osimertinib prolongs the survival of patients with &lt;i&gt;EGFR&lt;/i&gt;-mutant lung cancer; however, patients develop metastatic relapses, often to the brain. We identified a novel intracellular S100A9–ALDH1A1–RA signaling pathway that drives lethal brain relapse and can be targeted by pan-RAR antagonists to prevent cancer progression and prolong patient survival.&lt;/p&gt;&lt;p&gt;&lt;i&gt;This article is highlighted in the In This Issue feature, p. 873&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

• Supplementary Figure from Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in &lt;i&gt;EGFR&lt;/i&gt;-Mutant Lung Cancer

  2023-04-04

  preprintOpen accessSenior author

  Supplementary Figure from Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in &lt;i&gt;EGFR&lt;/i&gt;-Mutant Lung Cancer

  PublisherOA PDFDOI

• Data from Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in &lt;i&gt;EGFR&lt;/i&gt;-Mutant Lung Cancer

  2023-04-04

  preprintOpen accessSenior author

  &lt;div&gt;Abstract&lt;p&gt;The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in patients with &lt;i&gt;EGFR&lt;/i&gt;-mutant lung cancer, including those with brain metastases. However, despite striking initial responses, osimertinib-treated patients eventually develop lethal metastatic relapse, often to the brain. Although osimertinib-refractory brain relapse is a major clinical challenge, its underlying mechanisms remain poorly understood. Using metastatic models of &lt;i&gt;EGFR&lt;/i&gt;-mutant lung cancer, we show that cancer cells expressing high intracellular S100A9 escape osimertinib and initiate brain relapses. Mechanistically, S100A9 upregulates ALDH1A1 expression and activates the retinoic acid (RA) signaling pathway in osimertinib-refractory cancer cells. We demonstrate that the genetic repression of S100A9, ALDH1A1, or RA receptors (RAR) in cancer cells, or treatment with a pan-RAR antagonist, dramatically reduces brain metastasis. Importantly, S100A9 expression in cancer cells correlates with poor PFS in osimertinib-treated patients. Our study, therefore, identifies a novel, therapeutically targetable S100A9–ALDH1A1–RA axis that drives brain relapse.&lt;/p&gt;Significance:&lt;p&gt;Treatment with the EGFR TKI osimertinib prolongs the survival of patients with &lt;i&gt;EGFR&lt;/i&gt;-mutant lung cancer; however, patients develop metastatic relapses, often to the brain. We identified a novel intracellular S100A9–ALDH1A1–RA signaling pathway that drives lethal brain relapse and can be targeted by pan-RAR antagonists to prevent cancer progression and prolong patient survival.&lt;/p&gt;&lt;p&gt;&lt;i&gt;This article is highlighted in the In This Issue feature, p. 873&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

• Supplementary Figure from Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in &lt;i&gt;EGFR&lt;/i&gt;-Mutant Lung Cancer

  2023-04-04

  preprintOpen accessSenior author

  Supplementary Figure from Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in &lt;i&gt;EGFR&lt;/i&gt;-Mutant Lung Cancer

  PublisherDOI

• The Systemic Effects of Advanced Cancer

  2022-01-01 · 3 citations

  book1st authorCorresponding
  PublisherDOI

Recent grants

• Defining mechanisms of cancer chemoresistance and metastasis

  NIH · $737k · 2013–2017

• Modulating dietary zinc to prevent cachexia and improve survival in cancer

  NIH · $1.8M · 2019–2025

• NIH Grant K99CA172697

  NIH · $159k · 2013

Frequent coauthors

• Anup Biswas

  68 shared

• Courtney Coker

  Columbia University

  43 shared

• Denis C. Guttridge

  Medical University of South Carolina

  40 shared

• Wanchao Ma

  Columbia University

  31 shared

• Hanna Scholze

  28 shared

• Timothy James Zhong

  28 shared

• Michael G. B. Drew

  University of Reading

  23 shared

• Nirmalendu Biswas

  Centenary College of Louisiana

  23 shared

Labs

• Acharyya LabPI

Education

• Ph.D., Pathology and Cell Biology

  Columbia University

  2017

Awards & honors

• Shelanski Research Innovation Award in Pathology