About

Hatim Husain is a Clinical Professor of Medicine at UCSD Moores Cancer Center. His educational background includes training in Medical Oncology at Johns Hopkins University, Internal Medicine at the University of Southern California, and a Doctor of Medicine degree from Northwestern University. His research focuses on lung cancer, with a translational career dedicated to developing cancer therapeutic strategies in solid tumor malignancies. He is passionate about early drug development and aims to establish a translational laboratory for biomarker validation and drug testing in vitro and in vivo models, which can serve as a foundation for early phase clinical trials. Husain's work involves characterizing technology development in circulating tumor DNA and exploring its applications. His recent research includes understanding mechanisms of resistance to anti-EGFR therapies, immunogenic cell death in cancer cells, and the utility of circulating tumor DNA for monitoring treatment response. He has contributed to numerous publications in the field of lung cancer, focusing on genomic profiling, molecular mechanisms, and therapeutic strategies, making significant contributions to the understanding and management of non-small cell lung cancer.

Research topics

• Medicine
• Internal medicine
• Genetics
• Biology
• Oncology
• Computer Science
• Data Mining
• Cancer research
• Computational biology
• Botany
• Molecular biology
• Pathology

Selected publications

• PP01.15: Frontline Treatment Preferences Regarding Mode of Administration and Chemotherapy Among Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer in the United States

  Journal of Thoracic Oncology · 2026-05-01

  articleSenior author
  PublisherDOI

• Clinical strategies for lung cancer management: Recommendations from the Bridging the Gaps Lung Cancer Consensus Conference 2024

  Cancer · 2025-08-26 · 2 citations

  review

  Clinical practice guidelines for nonsmall cell lung cancer (NSCLC) and small cell lung cancer include recommendations based on high-level clinical trial evidence, but complex clinical questions are frequently seen in real-world practice that are not clearly answered by prospective trial data. To address these questions, the Bridging the Gaps Lung Cancer Consensus Conference 2024 (BtG LCCC 2024) convened to develop US-focused expert guidance for clinical situations in which level 1 evidence is lacking. At BtG LCCC 2024, a multidisciplinary expert panel discussed ongoing clinical issues in small cell lung cancer management, targeted therapy in EGFR-mutated NSCLC, management of early stage NSCLC, identification and management of non-EGFR oncogene-driven NSCLC, and use of immunotherapy in advanced/metastatic NSCLC. By using a modified Delphi process, 12 consensus recommendations were developed with the goal of providing guidance on the use of novel diagnostic methods and treatments for clinicians who manage lung cancer. This report reviews these areas of consensus and discusses ongoing questions about ways to apply current clinical evidence.

  PublisherDOI

• Author response: Regulation of lung cancer initiation and progression by the stem cell determinant Musashi

  2025-03-06

  peer-reviewOpen access
  PublisherDOI

• Diversity of BRAF mutations in non-small cell lung cancer and implications on treatment

  npj Precision Oncology · 2025-10-28 · 1 citations

  articleOpen accessSenior author

  Abstract The optimal treatment sequence in non-small cell lung cancer harboring class I BRAF mutations and atypical BRAF variants remains unclear. To better characterize therapeutic strategy, we retrospectively evaluated a multi-institutional cohort of BRAF -mutant NSCLC patients ( n = 97) and an independent clinico-genomic database ( n = 342), performed structural modeling, and conducted chemical screens of BRAF -mutant cell lines. Patients with class I BRAF mutation treated with BRAF–MEK inhibitors at any line of therapy had significantly greater median overall survival compared to those who did not receive BRAF–MEK inhibitors (40 vs 10 months, Log-rank p = 0.043). There, however, was no significant survival difference between patients treated with immune checkpoint inhibitors versus those not treated. Tumors with class II or III BRAF variants were significantly more likely to harbor concurrent MAPK pathway alterations relative to class I (Chi-Square p < 10 −4 ). Cell line studies identified genetic dependency on BRAF in class II cell lines without sensitivity to BRAF inhibitors, and dependency on EGFR in class III cell lines.

  PublisherOA PDFDOI

• Optimizing clinically actionable biomarker detection in advanced cancers by next generation sequencing (NGS) panel and specimen type.

  Journal of Clinical Oncology · 2025-05-28

  article1st authorCorresponding

  e15042 Background: There are many factors to consider when choosing the optimal NGS approach for successful biomarker testing. We present NGS data from 82 advanced solid tumor cases to illustrate how different NGS panels [small amplicon-based or comprehensive genomic profiling (CGP)] and specimen types [tumor tissue or circulating tumor DNA (ctDNA)] can influence detection of actionable variants for clinical decision-making. Methods: Matched ctDNA and tumor tissue specimens from 82 patients with advanced solid tumors were sequenced using the hybrid-capture TruSight™ Oncology 500 (TSO500) tissue and ctDNAv1 CGP (523 genes DNA, 55 genes RNA) assays and the amplicon-based oncoReveal™ Core LBx (104 genes) and multi-Cancer DNA (60 genes DNA) and RNA (18 genes) panels. Oncogenic variants were identified using the respective panels’ bioinformatics pipelines. Results: Concordance between tissue and ctDNA variant detection with TSO500 CGP was influenced by tumor type and ctDNA fraction. 6,360 total COSMIC variants were identified: 1,998 in ctDNA only, 642 in tissue only, and 3,720 in both. 52% of cases had ctDNA fractions < 1%, 30% had ctDNA fractions 1-10%, with 18% of cases > 10%. Colorectal (CRC) and non-small cell lung cancers (NSCLC) had the highest number of cases with ctDNA fraction > 1%. Higher ctDNA fraction correlated with greater concordance between tissue and ctDNA findings and increased sensitivity. Tissue-only variants were predominantly observed in cases with low ctDNA fractions, emphasizing the value of tissue testing in clinical scenarios with low estimated ctDNA fraction. ctDNA-only variants reflected tumor heterogeneity, indicating a maximized yield of oncogenic variant detection when testing both specimens. Select clinical cases further illustrate how testing results are influenced by NGS strategies. An actionable KRAS G12C variant was detected by all NGS panel and specimen types in CRC and NSCLC cases. However, a LANCL2-EGFR fusion was detected in tissue and ctDNA specimens from a gastric cancer case exclusively by the hybrid capture-based TSO500 panel, due to greater gene coverage and detection of novel fusions. Clinical relevance was confirmed by 6,000-8,000-fold higher EGFR expression levels, suggesting sensitivity to EGFR inhibitors. A PIK3CA E545K resistance mutation to EGFR inhibitors in a CRC case was found in ctDNA by both NGS panels but not in tissue, highlighting utility of ctDNA in capturing tumor heterogeneity. Conclusions: NGS panel and specimen selection must be tailored to the actionable variant classes specific to the individual’s tumor type and specific clinical scenarios impacting ctDNA fraction and tumor content. Hybrid-capture CGP panels can outperform small amplicon-based panels in detecting fusions and gene signatures, while ctDNA testing identifies tumor heterogeneity in clinical scenarios with higher estimated ctDNA fraction.

  PublisherDOI

• Molecular counting enables accurate and precise quantification of methylated ctDNA for tumor-naive cancer therapy response monitoring

  Scientific Reports · 2025-02-18 · 3 citations

  articleOpen access

  Personalized cancer treatment can significantly extend survival and improve quality of life for many patients, but accurate and real-time therapy response monitoring remains challenging. To overcome logistical and technical challenges associated with therapy response monitoring via imaging scans or assays that track the variant allele fraction (VAF) of somatic mutations in circulating tumor DNA (ctDNA), we developed a tumor-naive liquid biopsy assay that leverages Quantitative Counting Template (QCT) technology to accurately and precisely quantify methylated ctDNA (Northstar Response™). The assay achieves < 10% coefficient of variation at 1% tumor fraction, which is 2 × lower than tumor-naive, targeted-panel approaches using VAF. The assay accurately distinguishes 0.25% absolute changes in contrived tumor fraction (AUC > 0.94) and performs well in 12 solid tumor types. Finally, in a small cohort of patients with lung, colorectal, or pancreatic cancer, the assay detected changes in ctDNA methylation that correlate with clinical outcomes. With its precise quantification of ctDNA methylation, Northstar Response is a novel tool for therapy response monitoring with the potential to inform clinical decision making for cancer treatment.

  PublisherDOI

• Tepotinib in patients with MET exon 14 skipping non-small cell lung cancer

  Cancer Treatment Reviews · 2025-07-02 · 5 citations

  reviewOpen access

  The management of non-small cell lung cancer (NSCLC) has been transformed by the identification of specific therapies which target oncogenic drivers, including MET exon 14 (METex14) skipping, which occurs in 3-4% of patients. The development of selective MET inhibitors, such as tepotinib, has provided much-needed oral, targeted treatment options for these patients who otherwise have poor outcomes. In the largest trial involving patients with METex14 skipping NSCLC, the Phase II VISION study, tepotinib demonstrated robust and durable efficacy, which was especially notable when used in the first-line setting. Subgroup analyses demonstrated consistent efficacy in older and younger patients, Asian patients, and patients with brain metastases. The trial supported initial approval of tepotinib in Japan in 2020 and later in the US (accelerated approval: 2021; full approval: 2024) and many other countries worldwide. Here we delve into published literature on tepotinib, overview the mechanism of action and pharmacology, and provide a deep-dive into data from the pivotal VISION study, examining long-term outcomes, insights relevant for treatment sequencing, and biomarker analyses. We also discuss real-world data for tepotinib, indirect comparisons versus immuno- and/or chemotherapy, and provide experience from clinical practice, including guidance on managing adverse events, to provide a valuable aid for clinical practitioners.

  PublisherDOI

• Regulation of lung cancer initiation and progression by the stem cell determinant Musashi

  eLife · 2025-03-06

  articleOpen access

  Despite advances in therapeutic approaches, lung cancer remains the leading cause of cancer-related deaths. To understand the molecular programs underlying lung cancer initiation and maintenance, we focused on stem cell programs that are normally extinguished with differentiation but can be reactivated during oncogenesis. Here, we have used extensive genetic modeling and patient-derived xenografts (PDXs) to identify a dual role for Msi2: as a signal that acts initially to sensitize cells to transformation, and subsequently to drive tumor propagation. Using Msi reporter mice, we found that Msi2-expressing cells were marked by a pro-oncogenic landscape and a preferential ability to respond to Ras and p53 mutations. Consistent with this, genetic deletion of Msi2 in an autochthonous Ras/p53-driven lung cancer model resulted in a marked reduction of tumor burden, delayed progression, and a doubling of median survival. Additionally, this dependency was conserved in human disease as inhibition of Msi2 impaired tumor growth in PDXs. Mechanistically, Msi2 triggered a broad range of pathways critical for tumor growth, including several novel effectors of lung adenocarcinoma. Collectively, these findings reveal a critical role for Msi2 in aggressive lung adenocarcinoma, lend new insight into the biology of this disease, and identify potential new therapeutic targets.

  PublisherDOI

• Single-cell and spatial analysis reveals macrophage-T cell crosstalk in non-small cell lung cancer immunosuppression

  Translational Lung Cancer Research · 2025-09-01 · 5 citations

  articleOpen access

  Background: The tumor microenvironment (TME) is instrumental in facilitating immune evasion and promoting tumor progression in non-small cell lung cancer (NSCLC). However, the spatial heterogeneity and molecular interactions between immune and non-immune cells are not yet fully understood. This research amalgamated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomic data to examine the cellular composition, ligand-receptor (LR) interactions, and immunosuppressive mechanisms of NSCLC. Methods: ScRNA-seq was performed on NSCLC tumors and paired adjacent normal tissues to analyze immune and stromal cell heterogeneity. Spatial transcriptomics was applied to consecutive tissue sections to map the distribution of major cell types and their interactions. Cell clustering, a differential gene expression analysis, and LR interaction modeling were used to identify key immune regulatory pathways. In vitro co-culture experiments were performed for functional validation. Results: A total of 28,496 high-quality single cells were analyzed, and significant differences in immune cell composition between the tumor and normal tissues were found. The NSCLC tumors exhibited a notable increase in tumor-associated macrophages (TAMs) and fibroblasts, as well as a decrease in the presence of cytotoxic T cells and natural killer (NK) cells. Notably, spatial transcriptomics revealed that the TAMs were predominantly localized in the tumor cores, where they interacted with T cells via immunosuppressive LR pairs. The SPP1-CD44 and NECTIN2-TIGIT axes were identified as major immunosuppressive pathways, with the SPP1 secreted by the TAMs contributing to immune evasion. Additionally, the HLA-E-CD8B interactions were significantly upregulated, suggesting a potential mechanism of antigen presentation modulation. The functional validation showed that SPP1 overexpression (OE) enhanced PDCD1 and CD160 expression, further confirming its role in shaping the immunosuppressive microenvironment. Conclusions: This study established a high-resolution immune atlas of NSCLC, identifying novel macrophage-T cell interactions that drive immune suppression. Our findings suggest that targeting the SPP1-CD44, NECTIN2-TIGIT, and HLA-E-CD8B pathways may improve immune responses in NSCLC. These findings provide novel therapeutic targets and highlight the potential for combination immunotherapies to overcome macrophage-mediated immune evasion.

  PublisherDOI

• Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1

  Frontiers in Oncology · 2024-11-27 · 2 citations

  articleOpen access

  Introduction Matching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CGP) can simultaneously assess NSCLC tumors for hundreds of genomic biomarkers and markers for immunotherapy response, leading to quicker and more precise matches to therapeutics. Methods In this study, we performed CGP on 7,606 patients with advanced or metastatic NSCLC using the Illumina TruSight Oncology 500 (TSO 500) CGP assay to show its coverage and utility in detecting known and novel features of NSCLC. Results Testing revealed distinct genomic profiles of lung adenocarcinoma and squamous cell carcinomas and detected variants with a current targeted therapy or clinical trial in &amp;gt;72% of patient tumors. Known associations between genomic alterations and immunotherapy markers were observed including significantly lower TMB levels in tumors with therapy-associated alterations and significantly higher PD-L1 levels in tumors with ALK , MET , BRAF , or ROS1 driver mutations. Co-occurrence analysis followed by network analysis with gene module detection revealed known and novel co-occurrences between genomic alterations. Further, certain modules of genes with co-occurring genomic alterations had dose-dependent relationships with histology and increasing or decreasing levels of PD-L1 and TMB, suggesting a complex relationship between PD-L1, TMB, and genomic alterations in these gene modules. Discussion This study is the largest clinical study to date utilizing the TSO 500. It provides an opportunity to further characterize the landscape of NSCLC using this newer technology and show its clinical utility in detecting known and novel facets of NSCLC to inform treatment decision-making.

  PublisherOA PDFDOI

Frequent coauthors

• Brian Woodward

  University of California, San Diego

  59 shared

• Razelle Kurzrock

  Medical College of Wisconsin Cancer Center

  43 shared

• Scott M. Lippman

  32 shared

• Victor E. Velculescu

  University of Baltimore

  28 shared

• Geoffrey R. Oxnard

  26 shared

• Jillian Phallen

  Sidney Kimmel Comprehensive Cancer Center

  24 shared

• Russell W. Madison

  22 shared

• Ajaz Bulbul

  22 shared