Research

Rare Cancers

LSP researchers study rare cancers to uncover insights that can improve diagnosis and treatment.

By definition, each type of rare cancer affects few individuals - fewer than 40,000 Americans per year - yet as a whole, rare cancers are responsible for one-quarter of all cancer diagnoses and deaths[i]. LSP investigators apply the latest tissue profiling and systems pharmacology approaches to study several rare cancers including liposarcoma, leukemia, lymphoma, brain cancer, and rare melanoma subtypes. Much of our work on rare cancers is made possible by private foundations, which catalyze innovation to enable discoveries that can advance patient care.

Horwitz, S. M., Nirmal, A. J., Rahman, J., Xu, R., Drill, E., Galasso, N., Ganesan, N., Davey, T., Hancock, H., Perez, L., Maccaro, C., Bahgat, A., Marzouk, E., Cathcart, E., Moskowitz, A., Noy, A., Kumar, A., Jacobsen, E., Fisher, D. C., … Vardhana, S. A. (2024). Duvelisib plus romidepsin in relapsed/refractory T cell lymphomas: a phase 1b/2a trial. Nature Medicine, 30(9), 2517–2527. https://doi.org/10.1038/s41591-024-03076-6

Olesinski, E. A., Bhatia, K. S., Wang, C., Pioso, M. S., Lin, X. X., Mamdouh, A. M., Ng, S. X., Sandhu, V., Jasdanwala, S. S., Yilma, B., Bohl, S., Ryan, J. A., Malani, D., Luskin, M. R., Kallioniemi, O., Porkka, K., Adamia, S., Chng, W. J., Osato, M., … Bhatt, S. (2024). Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts. Blood Cancer Discovery, 5(3), 180–201. https://doi.org/10.1158/2643-3230.BCD-24-0001

Coy, S., Lee, J. S., Chan, S. J., Woo, T., Jones, J., Alexandrescu, S., Wen, P. Y., Sorger, P. K., Ligon, K. L., & Santagata, S. (2024). Systematic characterization of antibody-drug conjugate targets in central nervous system tumors. Neuro-Oncology, 26(3), 458–472. https://doi.org/10.1093/neuonc/noad205

Garcia, J. S., Kim, H. T., Murdock, H. M., Ansuinelli, M., Brock, J., Cutler, C. S., Gooptu, M., Ho, V. T., Koreth, J., Nikiforow, S., Romee, R., Shapiro, R., DeAngelo, D. J., Stone, R. M., Bat-Erdene, D., Ryan, J., Contreras, M. E., Fell, G., Letai, A., … Antin, J. H. (2024). Prophylactic maintenance with venetoclax/azacitidine after reduced-intensity conditioning allogeneic transplant for high-risk MDS and AML. Blood Advances, 8(4), 978–990. https://doi.org/10.1182/bloodadvances.2023012120

Haddox, C. L., Nathenson, M. J., Mazzola, E., Lin, J.-R., Baginska, J., Nau, A., Weirather, J. L., Choy, E., Marino-Enriquez, A., Morgan, J. A., Cote, G. M., Merriam, P., Wagner, A. J., Sorger, P. K., Santagata, S., & George, S. (2024). Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft Tissue Sarcomas: Clinical Outcomes and Biological Correlates. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. https://doi.org/10.1158/1078-0432.CCR-23-2250

Chen, W. C., Choudhury, A., Youngblood, M. W., Polley, M.-Y. C., Lucas, C.-H. G., Mirchia, K., Maas, S. L. N., Suwala, A. K., Won, M., Bayley, J. C., Harmanci, A. S., Harmanci, A. O., Klisch, T. J., Nguyen, M. P., Vasudevan, H. N., McCortney, K., Yu, T. J., Bhave, V., Lam, T.-C., … Raleigh, D. R. (2023). Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses. Nature Medicine, 29(12), 3067–3076. https://doi.org/10.1038/s41591-023-02586-z

Coy, S., Cheng, B., Lee, J. S., Rashid, R., Browning, L., Xu, Y., Chakrabarty, S. S., Yapp, C., Chan, S., Tefft, J. B., Scott, E., Spektor, A., Ligon, K. L., Baker, G. J., Pellman, D., Sorger, P. K., & Santagata, S. (2023). 2D and 3D multiplexed subcellular profiling of nuclear instability in human cancer [Preprint]. bioRxiv. https://doi.org/10.1101/2023.11.07.566063

Driver, J., Santagata, S., Bi, W. L., & Chi, J. H. (2023). Genomic analysis of spinal meningiomas: correlation with histopathological grade. Journal of Neurosurgery. Spine, 1–5. https://doi.org/10.3171/2023.6.SPINE23425

Cello, G., Patel, R. V., McMahon, J. T., Santagata, S., & Bi, W. L. (2023). Impact of H3K27 trimethylation loss in meningiomas: a meta-analysis. Acta Neuropathologica Communications, 11(1), 122. https://doi.org/10.1186/s40478-023-01615-9

Brastianos, P. K., Twohy, E., Geyer, S., Gerstner, E. R., Kaufmann, T. J., Tabrizi, S., Kabat, B., Thierauf, J., Ruff, M. W., Bota, D. A., Reardon, D. A., Cohen, A. L., De La Fuente, M. I., Lesser, G. J., Campian, J., Agarwalla, P. K., Kumthekar, P., Mann, B., Vora, S., … Galanis, E. (2023). BRAF-MEK inhibition in newly diagnosed papillary craniopharyngiomas. The New England Journal of Medicine, 389(2), 118–126. https://doi.org/10.1056/NEJMoa2213329

Nguyen, N., Wan, G., Ugwu-Dike, P., Alexander, N. A., Raval, N., Zhang, S., Jairath, R., Phillipps, J., Leung, B., Roster, K., Seo, J., Lu, C., Tang, K., Choi, M. S., DeSimone, M. S., Theodosakis, N., Amadife, M., Cox, N., Le, T. K., … Semenov, Y. R. (2023). Influence of melanoma type on incidence and downstream implications of cutaneous immune-related adverse events in the setting of immune checkpoint inhibitor therapy. Journal of the American Academy of Dermatology, 88(6), 1308–1316. https://doi.org/10.1016/j.jaad.2023.02.014

Perurena, N., Lock, R., Davis, R. A., Raghavan, S., Pilla, N. F., Ng, R., Loi, P., Guild, C. J., Miller, A. L., Sicinska, E., Cleary, J. M., Rubinson, D. A., Wolpin, B. M., Gray, N. S., Santagata, S., Hahn, W. C., Morton, J. P., Sansom, O. J., Aguirre, A. J., & Cichowski, K. (2023). USP9X mediates an acute adaptive response to MAPK suppression in pancreatic cancer but creates multiple actionable therapeutic vulnerabilities. Cell Reports. Medicine, 4(4), 101007. https://doi.org/10.1016/j.xcrm.2023.101007

Brastianos, P. K., Twohy, E. L., Gerstner, E. R., Kaufmann, T. J., Iafrate, A. J., Lennerz, J., Jeyapalan, S., Piccioni, D. E., Monga, V., Fadul, C. E., Schiff, D., Taylor, J. W., Chowdhary, S. A., Bettegowda, C., Ansstas, G., De La Fuente, M., Anderson, M. D., Shonka, N., Damek, D., … Galanis, E. (2023). Alliance A071401: phase II trial of focal adhesion kinase inhibition in meningiomas with somatic NF2 mutations. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 41(3), 618–628. https://doi.org/10.1200/JCO.21.02371

Driver, J., Hoffman, S. E., Tavakol, S., Woodward, E., Maury, E. A., Bhave, V., Greenwald, N. F., Nassiri, F., Aldape, K., Zadeh, G., Choudhury, A., Vasudevan, H. N., Magill, S. T., Raleigh, D. R., Abedalthagafi, M., Aizer, A. A., Alexander, B. M., Ligon, K. L., Reardon, D. A., … Bi, W. L. (2022). A molecularly integrated grade for meningioma. Neuro-Oncology, 24(5), 796–808. https://doi.org/10.1093/neuonc/noab213

Brastianos, P. K., Kim, A. E., Giobbie-Hurder, A., Lee, E. Q., Wang, N., Eichler, A. F., Chukwueke, U., Forst, D. A., Arrillaga-Romany, I. C., Dietrich, J., Corbin, Z., Moliterno, J., Baehring, J., White, M., Lou, K. W., Larson, J., de Sauvage, M. A., Evancic, K., Mora, J., … Santagata, S. (2022). Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas. Nature Communications, 13(1), 1325. https://doi.org/10.1038/s41467-022-29052-7

Koikawa, K., Kibe, S., Suizu, F., Sekino, N., Kim, N., Manz, T. D., Pinch, B. J., Akshinthala, D., Verma, A., Gaglia, G., Nezu, Y., Ke, S., Qiu, C., Ohuchida, K., Oda, Y., Lee, T. H., Wegiel, B., Clohessy, J. G., London, N., … Lu, K. P. (2021). Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy. Cell, 184(18), 4753-4771.e27. https://doi.org/10.1016/j.cell.2021.07.020

Jerby-Arnon, L., Neftel, C., Shore, M. E., Weisman, H. R., Mathewson, N. D., McBride, M. J., Haas, B., Izar, B., Volorio, A., Boulay, G., Cironi, L., Richman, A. R., Broye, L. C., Gurski, J. M., Luo, C. C., Mylvaganam, R., Nguyen, L., Mei, S., Melms, J. C., … Regev, A. (2021). Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma. Nature Medicine, 27(2), 289–300. https://doi.org/10.1038/s41591-020-01212-6

Touat, M., Li, Y. Y., Boynton, A. N., Spurr, L. F., Iorgulescu, J. B., Bohrson, C. L., Cortes-Ciriano, I., Birzu, C., Geduldig, J. E., Pelton, K., Lim-Fat, M. J., Pal, S., Ferrer-Luna, R., Ramkissoon, S. H., Dubois, F., Bellamy, C., Currimjee, N., Bonardi, J., Qian, K., … Ligon, K. L. (2020). Mechanisms and therapeutic implications of hypermutation in gliomas. Nature, 580(7804), 517–523. https://doi.org/10.1038/s41586-020-2209-9

Hemming, M. L., Nathenson, M. J., Lin, J.-R., Mei, S., Du, Z., Malik, K., Marino-Enriquez, A., Jagannathan, J. P., Sorger, P. K., Bertagnolli, M., Sicinska, E., Demetri, G. D., & Santagata, S. (2020). Response and mechanisms of resistance to larotrectinib and selitrectinib in metastatic undifferentiated sarcoma harboring oncogenic fusion of NTRK1. JCO Precision Oncology, 4, 79–90. https://doi.org/10.1200/po.19.00287

Koch, R., Christie, A. L., Crombie, J. L., Palmer, A. C., Plana, D., Shigemori, K., Morrow, S. N., Van Scoyk, A., Wu, W., Brem, E. A., Secrist, J. P., Drew, L., Schuller, A. G., Cidado, J., Letai, A., & Weinstock, D. M. (2019). Biomarker-driven strategy for MCL1 inhibition in T-cell lymphomas. Blood, 133(6), 566–575. https://doi.org/10.1182/blood-2018-07-865527

Foijer, F., Albacker, L. A., Bakker, B., Spierings, D. C., Yue, Y., Xie, S. Z., Davis, S., Lutum-Jehle, A., Takemoto, D., Hare, B., Furey, B., Bronson, R. T., Lansdorp, P. M., Bradley, A., & Sorger, P. K. (2017). Deletion of the MAD2L1 spindle assembly checkpoint gene is tolerated in mouse models of acute T-cell lymphoma and hepatocellular carcinoma. ELife, 6, e20873. https://doi.org/10.7554/eLife.20873

Brastianos, P. K., Taylor-Weiner, A., Manley, P. E., Jones, R. T., Dias-Santagata, D., Thorner, A. R., Lawrence, M. S., Rodriguez, F. J., Bernardo, L. A., Schubert, L., Sunkavalli, A., Shillingford, N., Calicchio, M. L., Lidov, H. G. W., Taha, H., Martinez-Lage, M., Santi, M., Storm, P. B., Lee, J. Y. K., … Santagata, S. (2014). Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nature Genetics, 46(2), 161–165. https://doi.org/10.1038/ng.2868

Clark, V. E., Erson-Omay, E. Z., Serin, A., Yin, J., Cotney, J., Ozduman, K., Avşar, T., Li, J., Murray, P. B., Henegariu, O., Yilmaz, S., Günel, J. M., Carrión-Grant, G., Yilmaz, B., Grady, C., Tanrikulu, B., Bakircioğlu, M., Kaymakçalan, H., Caglayan, A. O., … Günel, M. (2013). Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science (New York, N.Y.), 339(6123), 1077–1080. https://doi.org/10.1126/science.1233009

Cho, Y.-J., Tsherniak, A., Tamayo, P., Santagata, S., Ligon, A., Greulich, H., Berhoukim, R., Amani, V., Goumnerova, L., Eberhart, C. G., Lau, C. C., Olson, J. M., Gilbertson, R. J., Gajjar, A., Delattre, O., Kool, M., Ligon, K., Meyerson, M., Mesirov, J. P., & Pomeroy, S. L. (2011). Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 29(11), 1424–1430. https://doi.org/10.1200/JCO.2010.28.5148

Dias-Santagata, D., Lam, Q., Vernovsky, K., Vena, N., Lennerz, J. K., Borger, D. R., Batchelor, T. T., Ligon, K. L., Iafrate, A. J., Ligon, A. H., Louis, D. N., & Santagata, S. (2011). BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications. PloS One, 6(3), e17948. https://doi.org/10.1371/journal.pone.0017948

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Rare Cancers

LSP researchers study rare cancers to uncover insights that can improve diagnosis and treatment.

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