Photo of Daniel P. Cahill,  MD, PhD

Daniel P. Cahill, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-0884
Fax: (617) 724-0887

Daniel P. Cahill, MD, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Neurosurgery, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our long-term research goal is to advance basic scientific findings related to human brain tumors into improvements for our treatment of patients with these cancers. My clinical practice is focused at the MGH, where I devote a portion of my professional effort toward translational clinical activity in an academic environment, performing approximately 150 tumor neurosurgical procedures annually.

The larger portion of my professional effort is laboratory-based research activity focused on the study of malignant brain tumors to gain insight into the molecular genetic alterations that underlie their development, progression and treatment resistance. By understanding the mechanism by which these alterations drive formation of these cancers, therapeutic strategies to exploit this knowledge can be developed to improve outcomes for these patients.

We have made key observations regarding the molecular mechanisms of chemoresistance in human glioblastomas, over the last decade as combined radiation and alkylating chemotherapy temozolomide have become the standard-of-care. Our findings represented the first genomic evidence of mismatch-repair-mediated chemoresistance in any human tumor system, extending a well-established in-vitro model to the clinically relevant human treatment scenario. In the last year, our group has identified a tight linkage between IDH1 mutation in malignant astrocytomas and prolonged survival after surgical resection, a finding which can guide the personalization of therapy for patients with this type of brain tumor.

At the national level, our group performed molecular genetic analyses in the large randomized multi-national clinical trial of temozolomide dosing in glioblastoma, the Radiation Therapy Oncology Group 0525 study (RTOG-0525), contributing to the identification of molecular risk groups that will form the basis for future research on therapies for this disease. We have also participated at the national level on brain tumor committees with the aim to drive further innovation in the design of new clinical trials.

 

Publications

Powered by Harvard Catalyst
  • Olar A, Wani KM, Alfaro-Munoz KD, Heathcock LE, van Thuijl HF, Gilbert MR, Armstrong TS, Sulman EP, Cahill DP, Vera-Bolanos E, Yuan Y, Reijneveld JC, Ylstra B, Wesseling P, Aldape KD. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol 2015; 129:585-96. PubMed
  • Jones PS, Cahill DP, Brastianos PK, Flaherty KT, Curry WT. Ipilimumab and craniotomy in patients with melanoma and brain metastases: a case series. Neurosurg Focus 2015; 38:E5. PubMed
  • Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suvà ML, Regev A, Bernstein BE. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 2014. PubMed
  • Wakimoto H, Tanaka S, Curry WT, Loebel F, Zhao D, Tateishi K, Chen J, Klofas LK, Lelic N, Kim JC, Dias-Santagata D, Ellisen LW, Borger DR, Fendt SM, Vander Heiden MG, Batchelor TT, Iafrate AJ, Cahill DP, Chi AS. Targetable signaling pathway mutations are associated with malignant phenotype in IDH-mutant gliomas. Clin Cancer Res 2014. PubMed
  • Kim BY, Jiang W, Beiko J, Prabhu SS, Demonte F, Gilbert MR, Sawaya R, Aldape KD, Cahill DP, McCutcheon IE. Diagnostic discrepancies in malignant astrocytoma due to limited small pathological tumor sample can be overcome by IDH1 testing. J. Neurooncol. 2014. PubMed
  • Suvà ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, Riggi N, Chi AS, Cahill DP, Nahed BV, Curry WT, Martuza RL, Rivera MN, Rossetti N, Kasif S, Beik S, Kadri S, Tirosh I, Wortman I, Shalek AK, Rozenblatt-Rosen O, Regev A, Louis DN, Bernstein BE. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell 2014; 157:580-94. PubMed
  • Shankar GM, Taylor-Weiner A, Lelic N, Jones RT, Kim JC, Francis JM, Abedalthagafi M, Borges LF, Coumans JV, Curry WT, Nahed BV, Shin JH, Paek SH, Park SH, Stewart C, Lawrence MS, Cibulskis K, Thorner AR, Van Hummelen P, Stemmer-Rachamimov AO, Batchelor TT, Carter SL, Hoang MP, Santagata S, Louis DN, Barker FG, Meyerson M, Getz G, Brastianos PK, Cahill DP. Sporadic hemangioblastomas are characterized by cryptic VHL inactivation. Acta Neuropathol Commun 2015; 2:167. PubMed
  • Huse JT, Wallace M, Aldape KD, Berger MS, Bettegowda C, Brat DJ, Cahill DP, Cloughesy T, Haas-Kogan DA, Marra M, Miller CR, Nelson SJ, Salama SR, Soffietti R, Wen PY, Yip S, Yen K, Costello JF, Chang S. Where are we now? And where are we going? A report from the Accelerate Brain Cancer Cure (ABC2) low-grade glioma research workshop. 2014; 16:173-8. PubMed
  • Beiko J, Suki D, Hess KR, Fox BD, Cheung V, Cabral M, Shonka N, Gilbert MR, Sawaya R, Prabhu SS, Weinberg J, Lang FF, Aldape KD, Sulman EP, Rao G, McCutcheon IE, Cahill DP. IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. 2013; 16:81-91. PubMed
  • Bhat KP, Balasubramaniyan V, Vaillant B, Ezhilarasan R, Hummelink K, Hollingsworth F, Wani K, Heathcock L, James JD, Goodman LD, Conroy S, Long L, Lelic N, Wang S, Gumin J, Raj D, Kodama Y, Raghunathan A, Olar A, Joshi K, Pelloski CE, Heimberger A, Kim SH, Cahill DP, Rao G, Den Dunnen WF, Boddeke HW, Phillips HS, Nakano I, Lang FF, Colman H, Sulman EP, Aldape K. Mesenchymal differentiation mediated by NF-虜B promotes radiation resistance in glioblastoma. Cancer Cell 2013; 24:331-46. PubMed
  • Taylor JW, Chi AS, Cahill DP. Tailored therapy in diffuse gliomas: using molecular classifiers to optimize clinical management. Oncology (Huntingt) 2013; 27:504-14. PubMed
  • Dunn GP, Andronesi OC, Cahill DP. From genomics to the clinic: biological and translational insights of mutant IDH1/2 in glioma. Neurosurg Focus 2013; 34:E2. PubMed
  • Jones PS, Dunn GP, Barker FG, Curry WT, Hochberg FH, Cahill DP. Molecular genetics of low-grade gliomas: genomic alterations guiding diagnosis and therapeutic intervention. 11th Annual Frye-Halloran Brain Tumor Symposium. Neurosurg Focus 2013; 34:E9. PubMed
  • Dziurzynski K, Blas-Boria D, Suki D, Cahill DP, Prabhu SS, Puduvalli V, Levine N. Butterfly glioblastomas: a retrospective review and qualitative assessment of outcomes. J. Neurooncol. 2012; 109:555-63. PubMed
  • Likhacheva A, Pinnix CC, Parikh NR, Allen PK, McAleer MF, Chiu MS, Sulman EP, Mahajan A, Guha-Thakurta N, Prabhu SS, Cahill DP, Luo D, Shiu AS, Brown PD, Chang EL. Predictors of Survival in Contemporary Practice After Initial Radiosurgery for Brain Metastases. Int J Radiat Oncol Biol Phys 2012. PubMed
  • Raghunathan A, Olar A, Vogel H, Parker JR, Coventry SC, Debski R, Albarracin CT, Aldape KD, Cahill DP, Powell SZ, Fuller GN. Isocitrate dehydrogenase 1 R132H mutation is not detected in angiocentric glioma. Ann Diagn Pathol 2012; 16:255-9. PubMed
  • Olar A, Raghunathan A, Albarracin CT, Aldape KD, Cahill DP, Powell SZ, Goodman JC, Fuller GN. Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults. Ann Diagn Pathol 2012; 16:161-70. PubMed
  • Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH, Rodriguez FJ, Cahill DP, McLendon R, Riggins G, Velculescu VE, Oba-Shinjo SM, Marie SK, Vogelstein B, Bigner D, Yan H, Papadopoulos N, Kinzler KW. Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 2011; 333:1453-5. PubMed
  • Cahill DP, Barker FG, Davis KR, Kalva SP, Sahai I, Frosch MP. Case records of the Massachusetts General Hospital. Case 10-2010. A 37-year-old woman with weakness and a mass in the brain. N Engl J Med 2010; 362:1326-33. PubMed
  • Yip S, Miao J, Cahill DP, Iafrate AJ, Aldape K, Nutt CL, Louis DN. MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin Cancer Res 2009; 15:4622-9. PubMed
  • Cahill DP, Codd PJ, Batchelor TT, Curry WT, Louis DN. MSH6 inactivation and emergent temozolomide resistance in human glioblastomas. Clin Neurosurg 2009; 55:165-71. PubMed
  • Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, Batchelor TT, Futreal PA, Stratton MR, Curry WT, Iafrate AJ, Louis DN. Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res 2007; 13:2038-45. PubMed
  • Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR. Patterns of somatic mutation in human cancer genomes. Nature 2007; 446:153-8. PubMed
  • Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loeffler JS, Wen PY, Jain RK. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 2007; 11:83-95. PubMed
  • Hunter C, Smith R, Cahill DP, Stephens P, Stevens C, Teague J, Greenman C, Edkins S, Bignell G, Davies H, O'Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Butler A, Clements J, Cole J, Dicks E, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Richardson D, Shepherd R, Small A, Solomon H, Tofts C, Varian J, West S, Widaa S, Yates A, Easton DF, Riggins G, Roy JE, Levine KK, Mueller W, Batchelor TT, Louis DN, Stratton MR, Futreal PA, Wooster R. A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res 2006; 66:3987-91. PubMed
  • Wang Z, Cummins JM, Shen D, Cahill DP, Jallepalli PV, Wang TL, Parsons DW, Traverso G, Awad M, Silliman N, Ptak J, Szabo S, Willson JK, Markowitz SD, Goldberg ML, Karess R, Kinzler KW, Vogelstein B, Velculescu VE, Lengauer C. Three classes of genes mutated in colorectal cancers with chromosomal instability. Cancer Res 2004; 64:2998-3001. PubMed
Hide