Noncolorectal Gastrointestinal cancers (GI cancers) are a significant public health problem.
Current conventional therapeutic options, such as surgery, chemotherapy, radiotherapy, and targeted therapies, are not always highly effective in noncolorectal GI cancer patients, and the overall mortality remains a major issue.
Our group, led by Dr Teresa Macarulla (M.D. Ph.D.), is interested in seeking novel therapeutic strategies and associated predictive factors of noncolorectal GI cancers. One of our approaches is to combine biomarker discoveries and drug efficacy studies to better stratify noncolorectal GI cancer patients for personalized treatment.
Our clinical team has actively participated in developing molecular therapies targeting altered signaling pathways of pancreatic, gastric, and bile duct cancers (cholangiocarcinoma), among others. We have contributed to multiple phases I-III clinical trials examining novel anti-cancer strategies against noncolorectal GI cancers. Notably, the U.S Food and Drug Administration and the European Medicines Agency have approved several tested molecules for clinical use.
Moreover, using cancer patient-derived in vivo and ex vivo models, our preclinical team led by Dr Tian Tian (M.D. Ph.D.) is also studying the epigenetic and transcriptional features that can be used in gastric, pancreatic, and bile duct cancer diagnosis and treatment.
- Clinical development of novel therapeutic targets for noncolorectal GI cancers.
- Discovery and validation of novel prognostic biomarkers for noncolorectal GI cancers.
- Development and application of liquid biopsy protocols to monitor noncolorectal GI cancer progression and drug response.
- Design and development of investigator-initiated clinical trials, including Basket studies and participation in multidisciplinary/multinational consortia and collaborative research programs of excellence.
- Development of relevant in vivo and ex vivo preclinical noncolorectal GI cancers models.
- Study the molecular features of GI cancers (Cholangiocarcinoma and PDAC) using multi-omic approaches.
- Identification of transcriptional and epigenetic features in noncolorectal GI cancer diagnosis and treatment.
Group Leader
Teresa Macarulla
Preclinical team leader
Tian Tian
Clinical oncologists
Florian Castet
Carles Fabregat-Franco
Lab Manager
Jessica Querol
Ph.D. students
Carmen Escudero
Mariana Yáñez
Francheska Cadacio (FI SO Fellow)
Master students
Sofía Llorente
Joel Castro
- Verdaguer H, Sauri T, Acosta DA, Guardiola M, Sierra A, Hernando J, Nuciforo P, Miquel JM, Molero C, Peiro S, Serra-Camprubi Q, Villacampa G, Aguilar S, Vivancos A, Tabernero J, Dienstmann R, Macarulla T. ESMO Scale for Clinical Actionability of Molecular Targets driving targeted treatment in patients with cholangiocarcinoma. Clin Cancer Res. 2022. Epub 2022/01/20.
- Zhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DVT, Borad MJ, Bridgewater JA, Harris WP, Murphy AG, Oh DY, Whisenant JR, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Chamberlain CX, Aguado-Fraile E, Choe S, Wu B, Liu H, Gliser C, Pandya SS, Valle JW, Abou-Alfa GK. Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial. JAMA Oncol. 2021;7(11):1669-77.
- Javle M, Roychowdhury S, Kelley RK, Sadeghi S, Macarulla T, Weiss KH, Waldschmidt DT, Goyal L, Borbath I, El-Khoueiry A, Borad MJ, Yong WP, Philip PA, Bitzer M, Tanasanvimon S, Li A, Pande A, Soifer HS, Shepherd SP, Moran S, Zhu AX, Bekaii-Saab TS, Abou-Alfa GK. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol. 2021;6(10):803-15.
- Hecht JR, Lonardi S, Bendell J, Sim HW, Macarulla T, Lopez CD, Van Cutsem E, Munoz Martin AJ, Park JO, Greil R, Wang H, Hozak RR, Gueorguieva I, Lin Y, Rao S, Ryoo BY. Randomized Phase III Study of FOLFOX Alone or With Pegilodecakin as Second-Line Therapy in Patients With Metastatic Pancreatic Cancer That Progressed After Gemcitabine (SEQUOIA). J Clin Oncol. 2021;39(10):1108-18.
- Bockorny B, Macarulla T, Semenisty V, Borazanci E, Feliu J, Ponz-Sarvise M, Abad DG, Oberstein P, Alistar A, Munoz A, Geva R, Guillen-Ponce C, Fernandez MS, Peled A, Chaney M, Gliko-Kabir I, Shemesh-Darvish L, Ickowicz D, Sorani E, Kadosh S, Vainstein-Haras A, Hidalgo M. Motixafortide and Pembrolizumab Combined to Nanoliposomal Irinotecan, Fluorouracil, and Folinic Acid in Metastatic Pancreatic Cancer: The COMBAT/KEYNOTE-202 Trial. Clin Cancer Res. 2021;27(18):5020-7.
- Bilal F, Arenas EJ, Pedersen K, Martinez-Sabadell A, Nabet B, Guruceaga E, Vicent S, Tabernero J, Macarulla T, Arribas J. The Transcription Factor SLUG Uncouples Pancreatic Cancer Progression from the RAF-MEK1/2-ERK1/2 Pathway. Cancer Res. 2021;81(14):3849-61
- Tian TV, Sardina JL. Uncovering Sequence-Specific Transcription Factors Interacting with TET2. Methods Mol Biol. 2021;2272:239-50.
- Choi J, Lysakovskaia K, Stik G, Demel C, Soding J, Tian TV, Graf T, Cramer P. Evidence for additive and synergistic action of mammalian enhancers during cell fate determination. Elife. 2021;10. Epub 2021/03/27. doi: 10.7554/eLife.65381.
- Bockorny B, Semenisty V, Macarulla T, Borazanci E, Wolpin BM, Stemmer SM, Golan T, Geva R, Borad MJ, Pedersen KS, Park JO, Ramirez RA, Abad DG, Feliu J, Munoz A, Ponz-Sarvise M, Peled A, Lustig TM, Bohana-Kashtan O, Shaw SM, Sorani E, Chaney M, Kadosh S, Vainstein Haras A, Von Hoff DD, Hidalgo M. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med. 2020;26(6):878-85.
- Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(6):796-807.
- Tian TV, Vidal E, Graf T, Stik G. Identification of Enhancer-Promoter Contacts in Embryoid Bodies by Quantitative Chromosome Conformation Capture (4C). J Vis Exp. 2020(158).
- Stik G, Vidal E, Barrero M, Cuartero S, Vila-Casadesus M, Mendieta-Esteban J, Tian TV, Choi J, Berenguer C, Abad A, Borsari B, le Dily F, Cramer P, Marti-Renom MA, Stadhouders R, Graf T. CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response. Nat Genet. 2020;52(7):655-61.
- Macarulla T, Pazo-Cid R, Guillen-Ponce C, Lopez R, Vera R, Reboredo M, Munoz Martin A, Rivera F, Diaz Beveridge R, La Casta A, Martin Valades J, Martinez-Galan J, Ales I, Sastre J, Perea S, Hidalgo M. Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. J Clin Oncol. 2019;37(3):230-8.
- Tian TV, Di Stefano B, Stik G, Vila-Casadesus M, Sardina JL, Vidal E, Dasti A, Segura-Morales C, De Andres-Aguayo L, Gomez A, Goldmann J, Jaenisch R, Graf T. Whsc1 links pluripotency exit with mesendoderm specification. Nat Cell Biol. 2019;21(7):824-34.
- Sardina JL*, Collombet S*, Tian TV, Gomez A, Di Stefano B, Berenguer C, Brumbaugh J, Stadhouders R, Segura-Morales C, Gut M, Gut IG, Heath S, Aranda S, Di Croce L, Hochedlinger K, Thieffry D, Graf T. Transcription Factors Drive Tet2-Mediated Enhancer Demethylation to Reprogram Cell Fate. Cell Stem Cell. 2018;23(5):727-41 e9.
- Delliaux C*, Tian TV*, Bouchet M, Fradet A, Vanpouille N, Flourens A, Deplus R, Villers A, Leroy X, Clezardin P, de Launoit Y, Bonnelye E, Duterque-Coquillaud M. TMPRSS2:ERG gene fusion expression regulates bone markers and enhances the osteoblastic phenotype of prostate cancer bone metastases. Cancer Lett. 2018;438:32-43.
- Ruetz T, Pfisterer U, Di Stefano B, Ashmore J, Beniazza M, Tian TV, Kaemena DF, Tosti L, Tan W, Manning JR, Chantzoura E, Ottosson DR, Collombet S, Johnsson A, Cohen E, Yusa K, Linnarsson S, Graf T, Parmar M, Kaji K. Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming. Cell Stem Cell. 2017;21(6):791-805 e9.
- Di Giacomo V, Tian TV, Mas A, Pecoraro M, Batlle-Morera L, Noya L, Martin-Caballero J, Ruberte J, Keyes WM. DeltaNp63alpha promotes adhesion of metastatic prostate cancer cells to the bone through regulation of CD82. Oncogene. 2017;36(31):4381-92.
- Epigenomic characterization of cholangiocarcinoma. Fundació Marató TV3. 2020–2023
- Proteínas de fusión BRD-NUT en el carcinoma de línea media NUT: del diagnóstico al tratamiento. Plan Estatal de I+D+i Orientada a los Retos de la Sociedad, Ministerio de Ciencia e Innovación. 2020-2023
- Characterization of fusion protein BRD-NUT in NUT midline carcinoma. Fundación AECC. 2020-2022
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