SUMMARY
Farhad Kosari, Ph.D., has a multidisciplinary background spanning bioinformatics and molecular biology. Dr. Kosari uses omics technologies to address clinically significant challenges in oncology. He focuses on mesothelioma, small cell lung cancer and lung adenocarcinomas with neuroendocrine differentiation characterized by high expression of ASCL1 (A+AD).
While immune checkpoint inhibitors were recently approved by the Food and Drug Administration to treat unresectable pleural mesothelioma, the disease remains highly aggressive. Despite traditional therapies such as chemotherapy and surgery, mesothelioma continues to be a recalcitrant malignancy with a median overall survival of 12 to 18 months.
Small cell lung cancer is another aggressive thoracic malignancy that claims 30,000 lives in the United States each year. It is found almost exclusively among people who are heavy smokers. For decades, the cornerstone of treatment was limited to chemoradiation therapy.
Recent clinical trials demonstrated that adding immune checkpoint inhibitors to these regimens provides a modest survival benefit of approximately two months. However, despite this new standard of care, small cell lung cancer remains a recalcitrant malignancy with a median survival of 12.3 months. This underscores the urgent need for new therapies.
Similarly, A+AD is another aggressive cancer linked to smoking. Elevated expression of neuroendocrine transcription factor ASCL1 creates specific tumor vulnerabilities that are largely underappreciated and therapeutically untapped.
Dr. Kosari also has a long-standing interest in the cancer field effect, also known as field cancerization. This phenomenon refers to molecular changes found in morphologically benign tissue adjacent to a tumor. These changes are not present in healthy, cancer-free tissue.
Focus areas
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Determinants of immune checkpoint inhibitor response in mesotheliomas. Dr. Kosari and his team develop multi-omics models to identify patients likely to benefit from treatment with immune checkpoint inhibitors.
Having previously shown that combining chromosomal rearrangements with antigen presentation signatures yields highly predictive models — particularly when using CD8 mRNA as a surrogate for T-cell trafficking — the team has since expanded its scope to the T-cell repertoire. The group found that tumors enriched with circulating T-cell clones — shared CDR3 regions between tissue and serum — confer a significant survival advantage. The team's current work focuses on refining antigen presentation signatures and identifying the salient CDR3 features of responders to enhance model accuracy.
Parallel to this, Dr. Kosari and his team are investigating the noncoding regulatory landscape. Using a competing endogenous RNA (ceRNA) framework, they identified coordinated cross talk among ceRNA networks targeted by overexpressed microRNAs in responders. They are now refining this computational approach by incorporating binding site affinity variations driven by the specific nucleotide composition of microRNA response elements.
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New therapies for small cell lung cancer and A+AD. Dr. Kosari and his team have examined a cohort of patients with small cell lung cancer who survived for many years and often more than a decade despite the aggressive nature of the disease. Their analysis revealed that these long-term survivors possess a hot tumor microenvironment characterized by high immune cell infiltration.
The team identified a strong tumor-to-blood CXCL9 concentration gradient (∇C9) in these patients — a feature notably absent in those with poor outcomes. Because this gradient is a primary driver for immune cell recruitment, the team is now investigating new approaches to warm small cell lung cancer tumors by boosting ∇C9.
Additionally, their work in A+AD led to the discovery of RET oncogene elevations linked to poor survival. Dr. Kosari and his team are currently evaluating the therapeutic potential of blocking RET signaling in these patients.
- Prostate cancer field effect. Dr. Kosari's earlier work demonstrated transcriptional changes in morphologically benign tissues that were consistent with the expression profiles of adjacent prostate cancer. More recently, Dr. Kosari's team demonstrated that the high-grade prostatic intraepithelial neoplasia gene expression profile correlates with prostate cancer Gleason score and points to early alterations in the immune microenvironment. Based on these findings, ongoing research aims to develop new strategies for prostate cancer prevention.
Significance to patient care
By working with medical teams that treat cancer, Dr. Kosari's research focuses on issues that affect patient care. By studying patient data using multi-omics tools, Dr. Kosari develops new ways to find and treat the disease.
Professional highlights
- Member, IEEE Engineering in Medicine and Biology Society, 2025-present.
- Member, American Association for Cancer Research, 2013-present.
- Review panel member, National Cancer Institute, 2023-2024.
- Topic editor, International Journal of Molecular Sciences, 2020.
- Career Development Award, Mayo Clinic Prostate Cancer Specialized Program of Research Excellence, Mayo Clinic, 2007-2008.