Junaid Arshad

Interests

Research

Dr. Arshad's Clinical and Research focus targets mainly the Upper GI Oncology including Gastrointestinal Stromal Tumors, Gastric Cancers, Esophageal Cancers and Neuroendocrine Tumors. He is a part of several industry and investigator initiated clinical trials and has contributed to several peer reviewed publications. His prior research focuses on the use of biomarkers such as circulating tumor DNA (ctDNA) in the diagnosis, treatment and surveillance of Gastrointestinal Stromal Tumors. He has expanded his areas of research interest to include other disease modalities such as Neuroendocrine Tumor.

Courses

No activities entered.

Scholarly Contributions

Journals/Publications

• Arshad, J., Rao, A., Repp, M. L., Rao, R., Wu, C., & Merchant, J. L. (2024). Myeloid-Derived Suppressor Cells: Therapeutic Target for Gastrointestinal Cancers. International Journal of Molecular Sciences, 25(5), 2985. doi:10.3390/ijms25052985
• Arshad, J., Rao, A., Repp, M. L., Rao, R., Wu, C., & Merchant, J. L. (2024). Myeloid-Derived Suppressor Cells: Therapeutic Target for Gastrointestinal Cancers. International journal of molecular sciences, 25(5).
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  Gastrointestinal cancers represent one of the more challenging cancers to treat. Current strategies to cure and control gastrointestinal (GI) cancers like surgery, radiation, chemotherapy, and immunotherapy have met with limited success, and research has turned towards further characterizing the tumor microenvironment to develop novel therapeutics. Myeloid-derived suppressor cells (MDSCs) have emerged as crucial drivers of pathogenesis and progression within the tumor microenvironment in GI malignancies. Many MDSCs clinical targets have been defined in preclinical models, that potentially play an integral role in blocking recruitment and expansion, promoting MDSC differentiation into mature myeloid cells, depleting existing MDSCs, altering MDSC metabolic pathways, and directly inhibiting MDSC function. This review article analyzes the role of MDSCs in GI cancers as viable therapeutic targets for gastrointestinal malignancies and reviews the existing clinical trial landscape of recently completed and ongoing clinical studies testing novel therapeutics in GI cancers.
• Chakrabarti, J., Adhikary, P., Wang, J., Sohal, D., Ahmad, S. A., Arshad, J., Scott, A. J., Shroff, R. T., & Zavros, Y. (2024). Abstract 1582: Cabozantinib changes the tumor microenvironment to increase the efficacy of immunotherapy in refractory metastatic pancreatic ductal adenocarcinoma. Cancer Research, 84(6_Supplement), 1582-1582. doi:10.1158/1538-7445.am2024-1582
• Mahmud, M., Munjal, A., Savani, M., Win, H., Rozell, U., & Arshad, J. (2024). Biomarker Testing and Role of Tyrosine Kinase Inhibitors and Immunotherapy for Esophageal Squamous Cell Carcinoma. Foregut: The Journal of the American Foregut Society. doi:10.1177/26345161241238748
• Mahmud, M., Munjal, A., Savani, M., Win, H., Rozell, U., & Arshad, J. (2024). Biomarker Testing and Role of Tyrosine Kinase Inhibitors and Immunotherapy for Esophageal Squamous Cell Carcinoma. Foregut, 4(4). doi:10.1177/26345161241238748
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  Esophageal squamous cell carcinoma (ESCC) constitutes an aggressive subset of esophageal cancers that portends a poor prognosis. Management of ESCC has been historically challenging due to the limited effective therapeutic options. Broadening our understanding of the molecular landscape and identifying reliable biomarkers are essential in early detection, monitoring disease response and advancing treatment strategies. Recently, immunotherapy and tyrosine kinase inhibitors have changed the treatment algorithm of ESCC. In this review, we explore the molecular landscape and biomarkers that can aid in the management of ESCC and discuss the role of immunotherapy and tyrosine kinase inhibitors in the treatment of ESCC.
• Rao, A., Rao, R., Taylor, M. K., Khreiss, M., & Arshad, J. (2024). Concurrent Stage III Unresectable Duodenal Adenocarcinoma and Metastatic Gastrointestinal Stromal Tumor Treated With Combination of Imatinib and mFOLFIRI. Cureus, 16(4), e58248.
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  Cases of concurrent duodenal adenocarcinoma and gastrointestinal stromal tumors (GISTs) are rare, and only a few have been reported. While some cases of other synchronous primary tumors with GIST have been reported, no shared mutations have been consistently found, creating challenges in selecting chemotherapy in cases of inoperable tumors. Here, we presented a case of a stage IIIA locally advanced/unresectable duodenal adenocarcinoma with concurrent metastatic small bowel GIST successfully being treated with combined imatinib and modified folinic acid, 5-fluorouracil, and irinotecan (mFOLFIRI) regimen.
• Young, S., Hannallah, J., Goldberg, D., Khreiss, M., Shroff, R., Arshad, J., Scott, A., & Woodhead, G. (2024). Liver-Directed Therapy Combined with Systemic Therapy: Current Status and Future Directions. Seminars in Interventional Radiology, 40(6). doi:10.1055/s-0043-1777711
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  In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.
• Del Rivero, J., Perez, K., Kennedy, E. B., Mittra, E. S., Vijayvergia, N., Arshad, J., Basu, S., Chauhan, A., Dasari, A. N., Bellizzi, A. M., Gangi, A., Grady, E., Howe, J. R., Ivanidze, J., Lewis, M., Mailman, J., Raj, N., Soares, H. P., Soulen, M. C., , White, S. B., et al. (2023).

  Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline

  . Journal of Clinical Oncology, 41(32), 5049-5067. doi:10.1200/jco.23.01529
• Young, S., Hannallah, J., Goldberg, D., Khreiss, M., Shroff, R., Arshad, J., Scott, A., & Woodhead, G. (2023). Liver-Directed Therapy Combined with Systemic Therapy: Current Status and Future Directions. Seminars in interventional radiology, 40(6), 515-523.
  More info

  In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.
• Arshad, J., Bialick, S., Rose, B. E., Espejo-Freire, A. P., Barreto Coelho, P., Costa, P. A., Campoverde, L., Drusbosky, L., Serrano, C., George, S., Bauer, S., Goel, N., Venkat, S., Dhir, A., Jonczak, E., D'Amato, G. Z., & Trent, J. C. (2022). KIT resistance mutations identified by circulating tumor DNA and treatment outcomes in advanced gastrointestinal stromal tumor.. Journal of Clinical Oncology, 40(16_suppl), 11514-11514. doi:10.1200/jco.2022.40.16_suppl.11514
• Arshad, J., Costa, P. A., Barreto-Coelho, P., Valdes, B. N., & Trent, J. C. (2021). Immunotherapy Strategies for Gastrointestinal Stromal Tumor. Cancers, 13(14).
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  Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. The management of locally advanced or metastatic unresectable GIST involves detecting KIT, PDGFR, or other molecular alterations targeted by imatinib and other tyrosine kinase inhibitors. The role of immunotherapy in soft tissue sarcomas is growing fast due to multiple clinical and pre-clinical studies with no current standard of care. The potential therapies include cytokine-based therapy, immune checkpoint inhibitors, anti-KIT monoclonal antibodies, bi-specific monoclonal antibodies, and cell-based therapies. Here we provide a comprehensive review of the immunotherapeutic strategies for GIST.
• Espejo-Freire, A. P., Elliott, A., Rosenberg, A., Costa, P. A., Barreto-Coelho, P., Jonczak, E., D'Amato, G., Subhawong, T., Arshad, J., Diaz-Perez, J. A., Korn, W. M., Oberley, M. J., Magee, D., Dizon, D., von Mehren, M., Khushman, M. M., Hussein, A. M., Leu, K., & Trent, J. C. (2021). Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis. Cancers, 13(19).
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  We performed a retrospective analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin in a cohort of 143 cases. Primary sites were head and neck (31%), breast (22%), extremity (11%), viscera (20%), skin at other locations (8%), and unknown (9%). All cases had Next Generation Sequencing (NGS) data with a 592 gene panel, and 53 cases had Whole Exome Sequencing (WES) data, which we used to study the microenvironment phenotype. The immunotherapy (IO) response biomarkers Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), and PD-L1 status were the most frequently encountered alteration, present in 36.4% of the cohort and 65% of head and neck AS (H/N-AS) ( < 0.0001). In H/N-AS, TMB-High was seen in 63.4% of cases ( < 0.0001) and PDL-1 positivity in 33% of cases. The most common genetic alterations were (29%), amplification (23%), (17%), (16%), and (13%). H/N-AS cases had predominantly mutations in (50.0%, = 0.0004), (40.5%, < 0.0001), and (33.3%, = 0.5875). In breast AS, leading alterations were amplification (63.3%, < 0.0001), (16.1%, = 0.0377), and (16.1%, = 0.2352). At other sites, conclusions are difficult to generate due to the small number of cases. A microenvironment with a high immune signature, previously associated with IO response, was evenly distributed in 13% of the cases at different primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS.
• Arshad, J. (2020). Progress in determining response to treatment in gastrointestinal stromal tumor. Expert Review of Anticancer Therapy, 2020(issue 4), 279-288. doi:https://doi.org/10.1080/14737140.2020.1745068
• Arshad, J., Roberts, A., Ahmed, J., Cotta, J., Pico, B. A., Kwon, D., & Trent, J. C. (2020). Utility of Circulating Tumor DNA in the Management of Patients With GI Stromal Tumor: Analysis of 243 Patients. JCO precision oncology, 4, 66-73.
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  GI stromal tumor (GIST) is the most common sarcoma of the GI tract. Management of patients with GIST is determined by , , or other genomic alterations. Tissue-based next-generation sequencing (NGS) analysis is the standard approach for diagnosis, prognosis, and treatment selection. However, circulating tumor DNA (ctDNA)-based NGS is a novel and noninvasive alternative.
• Ali, R., Arshad, J., Palacio, S., & Mudad, R. (2019). Brigatinib for -positive metastatic non-small-cell lung cancer: design, development and place in therapy. Drug design, development and therapy, 13, 569-580.
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  Despite the benefits of first and second generation anaplastic lymphoma kinase () inhibitors in the management of -rearranged advanced non-small-cell lung cancer (NSCLC), the development of acquired resistance poses an ongoing dilemma. Brigatinib has demonstrated a wider spectrum of preclinical activity against crizotinib-resistant mutant advanced NSCLC. The current review narrates a brief history of tyrosine kinases, the development and clinical background of brigatinib (including its pharmacology and molecular structure) and its use in -positive NSCLC.
• Arshad, J., Roberts, A., Ahmed, J., Cotta, J., Pico, B., Kwon, D., & Trent, J. (2019). Utility of circulating tumor DNA in the management of patients with GI stromal tumor: Analysis of 243 patients. JCO Precision Oncology, 3. doi:10.1200/PO.19.00253
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  PURPOSE GI stromal tumor (GIST) is the most common sarcoma of the GI tract. Management of patients with GIST is determined by KIT, PDGFRA, or other genomic alterations. Tissue-based next-generation sequencing (NGS) analysis is the standard approach for diagnosis, prognosis, and treatment selection. However, circulating tumor DNA (ctDNA)-based NGS is a novel and noninvasive alternative. METHODS ctDNA sequencing results were evaluated in blood samples from 243 de-identified patients within the Guardant360 database. Under an approved institutional review board protocol, a retrospective analysis was performed on 45 single-institution patients. RESULTS Of 243 patients, 114 (47%) were women, and the median age was 59 years (range, 17-90 years). Patients with no alterations and variations of uncertain significance were excluded. Of the 162 patients with known pathogenic mutations, KIT was the most common (56%), followed by NF (7%), PDGFRA (6%), PI3KCA (6%), KRAS (5%), and others (6%). Most tumors harbored an actionable KIT or PDGFRA mutation. Our institutional cohort (n = 45) had 16 (35%) KIT exon 11 mutations, 3 (6%) KIT exon 9 mutations, and 1 (2%) PDGFRA mutation detected on ctDNA. Resistance mutations were observed in KIT exon 17 (8 patients), exon 13 (3 patients), and in both (3 patients). Our comparison of ctDNA with tissue NGS revealed a positive predictive value (PPV) of 100%. Failure of concordance was observed in patients with localized or low disease burden. From the time of ctDNA testing, the median overall survival was not reached, whereas the median progressionfree survival was 7 months. CONCLUSION ctDNA provides a rapid, noninvasive analysis of current mutations with a high PPV for patients with metastatic GIST. ctDNA-based testing may help to define the optimal choice of therapy on the basis of resistance mutations and should be studied prospectively.
• Palacio, S., Pontes, L., Prado, E., Arshad, J., Ali, R., Piha, T., Bacchi, C. E., Mudad, R., & Lopes, G. (2019). Mutation Testing: Changing Patterns of Molecular Testing in Brazil. The oncologist, 24(4), e137-e141.
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  In Brazil, cancer is the second most common cause of death. Most patients in resource-limited countries are diagnosed in advanced stages. Current guidelines advocate for mutation testing in all patients with metastatic adenocarcinoma. Tyrosine kinase inhibitors are recommended in patients with advanced or metastatic disease harboring sensitizing mutations. In Brazil, there are limited data regarding the frequency of testing and the changes in patterns of testing overtime.
• Onuoha, C., Arshad, J., Astle, J., Xu, M., & Halene, S. (2016). Novel Developments in Leukopenia and Pancytopenia. Primary care, 43(4), 559-573.
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  Cytopenias are not disease entities in and of themselves; rather, they are the expression of various underlying disease processes. Careful attention to details in patients' presentation, careful history and examination, as well as attention to the ancillary parameters of the complete blood count with a peripheral blood smear can point the clinician toward the appropriate workup. Causes of cytopenias can be inherited or acquired; the latter include medication related, autoimmune, or neoplastic causes. Emergencies need to be recognized in a timely fashion and expert consultation obtained.

Presentations

• Arshad, J. (2019, November/Fall). Review of genetic alterations in Sarcoma patients of Hispanic Ethnicity: Analysis of

  167 patients, A single institution experience. Connective Tissue Oncology Society (CTOS). Tokyo, Japan: CTSOS.

• Arshad, J. (2018, November/Fall). Utility of Circulating Tumor DNA in the Management of Patients with GIST: Analysis

  of 184 patients. Connective Tissue Oncology Society (CTOS). Rome, Italy: CTOS.

Poster Presentations

• Arshad, J. (2019, April/Spring). Analysis of Mutations in the primary Mucinous Adenocarcinoma of Lung analysis of

  26 patients. Florida Society of Clinical Oncology (FLASCO). Kissimmee: FLASCO.

• Arshad, J. (2019, October/Fall). Utility of ctDNA in the management of Gastrointestinal Stromal Tumors: Analysis of

  243 patients. International Society of Gastroenterology Oncology (ISGO). Nashville, TN: ISGO.

• Arshad, J. (2016, June/Summer). Follicular Lymphoma Presenting as Bilateral Pleural Effusion. Waterbury Research Day. Connecticut: Yale School of Medicine.
• Arshad, J. (2016, June/Summer). Intrahepatic Cholestasis, A severe form of Sickle Cell Hepatopathy. Waterbury Research Day. Connecticut: Yale School of Medicine.
• Arshad, J. (2015, Fall/Winter). Extra nodal NK Cell Lymphoma Nasal Type,. American College of Physicians (ACP). Connecticut: ACP.
• Arshad, J. (2015, May/Spring). Small Bowel Lymphoma in Celiac Disease. Waterbury Research Day. Connecticut: Yale School of Medicine.
• Arshad, J. (2015, October/Fall). An Unusual Case of Upper GI Bleeding. American College of Physicians (ACP). Connecticut: ACP.
• Arshad, J. (2015, October/Fall). Evaluation of patient with Pyoderma Gangrenosum. American College of Physicians (ACP). Connecticut: ACP.
• Arshad, J. (2014, Fall/October). Takotsubo Cardiomyopathy. American College of Physicians (ACP) Connecticut ChapterACP.