Drug Resistance and the Role of Combination Chemotherapy in Improving Patient Outcomes
TLDR
The aim of this paper is to review mechanisms of resistance to common chemotherapy agents and to consider current combination treatment options for heavily pretreated and/or drug-resistant patients with MBC.Abstract:
Resistance to cancer chemotherapy is a common phenomenon especially in metastatic breast cancer (MBC), a setting in which patients typically have had exposure to multiple lines of prior therapy The subsequent development of drug resistance can result in rapid disease progression during or shortly after completion of treatment Moreover, cross-class multidrug resistance limits patient treatment choices, particularly in a setting where treatments options are few One attempt to minimize the impact of drug resistance has been the concurrent use of two or more chemotherapy agents with unrelated mechanisms of action and differing modes of drug resistance, with the intent of blocking the development of multiple intracellular escape pathways essential for tumor survival Within the past decade, an array of mechanistically diverse agents has augmented the list of combination regimens that may be both synergistic and efficacious in pretreated MBC The aim of this paper is to review mechanisms of resistance to common chemotherapy agents and to consider current combination treatment options for heavily pretreated and/or drug-resistant patients with MBCread more
Citations
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The multi-factorial nature of clinical multidrug resistance in cancer.
Yehuda G. Assaraf,Anamaria Brozovic,Ana Cristina Gonçalves,Dana Jurkovicova,Aija Linē,Miguel Machuqueiro,Simona Saponara,Ana Bela Sarmento-Ribeiro,Cristina P.R. Xavier,M. Helena Vasconcelos,M. Helena Vasconcelos +10 more
TL;DR: This review aims to bring together these multidisciplinary and interdisciplinary features of MDR cancers by deciphering the molecular mechanisms underlying anticancer drug resistance, to pave the way towards the development of novel precision medicine treatment modalities that are able to surmount distinct and well-defined mechanisms of antic cancer drug resistance.
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Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing
Mei-Chong Wendy Lee,Fernando J. Lopez-Diaz,Shahid Y. Khan,Muhammad Tariq,Yelena Dayn,Charles J. Vaske,Amie Radenbaugh,Hyunsung John Kim,Beverly M. Emerson,Nader Pourmand +9 more
TL;DR: Single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy.
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A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4).
Miguel Martin,Arlene Chan,L.Y. Dirix,Joyce O'Shaughnessy,Roberto Hegg,Alexey Manikhas,Mikhail Shtivelband,Petr Krivorotko,N. Batista López,M. Campone,M. Ruiz Borrego,Qamar J. Khan,JT Beck,M. Ramos Vazquez,Patrick Urban,S. Goteti,E. Di Tomaso,Cristian Massacesi,Suzette Delaloge +18 more
TL;DR: Addition of buparlisib to paclitaxel did not improve PFS in the full or PI3K pathway-activated study population, and the trial was stopped for futility at the end of phase II.
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Mechanisms Underlying the Action and Synergism of Trastuzumab and Pertuzumab in Targeting HER2-Positive Breast Cancer
TL;DR: A thorough understanding of the molecular mechanisms underlying the action and synergism of trastuzumab and pertuzumAB is essential for moving forward to achieve high efficacy in treating HER2-positive breast cancer.
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Sulforaphane enhances the anticancer activity of taxanes against triple negative breast cancer by killing cancer stem cells
Joseph Burnett,Gi Lim,Yanyan Li,Ronak B. Shah,Rebekah Lim,Hayley J. Paholak,Sean P. McDermott,Lichao Sun,Yasuhiro Tsume,Shuhua Bai,Max S. Wicha,Duxin Sun,Tao Zhang +12 more
TL;DR: The results suggest that treatment of TNBCs with cytotoxic chemotherapy would be greatly benefited by the addition of sulforaphane to prevent expansion of and eliminate breast CSCs.
References
More filters
Journal ArticleDOI
Molecular portraits of human breast tumours
Charles M. Perou,Therese Sørlie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,Christian A. Rees,Jonathan R. Pollack,Douglas T. Ross,Hilde Johnsen,Lars A. Akslen,Øystein Fluge,Alexander Pergamenschikov,Cheryl A. Williams,Shirley Zhu,Per Eystein Lønning,Anne Lise Børresen-Dale,Patrick O. Brown,David Botstein +17 more
TL;DR: Variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals were characterized using complementary DNA microarrays representing 8,102 human genes, providing a distinctive molecular portrait of each tumour.
Journal ArticleDOI
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
Therese Sørlie,Charles M. Perou,Robert Tibshirani,Turid Aas,Stephanie Geisler,Hilde Johnsen,Trevor Hastie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,T. Thorsen,Hanne Quist,John C. Matese,Patrick O. Brown,David Botstein,Per Eystein Lønning,Anne Lise Børresen-Dale +16 more
TL;DR: Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.
Journal ArticleDOI
Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2
Dennis J. Slamon,Brian Leyland-Jones,Steven Shak,Hank Fuchs,Virginia E. Paton,Alex Bajamonde,Thomas Fleming,Wolfgang Eiermann,Janet M. Wolter,Mark D. Pegram,José Baselga,Larry Norton +11 more
TL;DR: The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression, a higher rate of objective response, a longer duration of response, and a lower rate of death at 1 year.
Journal ArticleDOI
Repeated observation of breast tumor subtypes in independent gene expression data sets
Therese Sørlie,Robert Tibshirani,Joel S. Parker,Trevor Hastie,James Stephen Marron,Andrew B. Nobel,Shibing Deng,Hilde Johnsen,Robert Pesich,Stephanie Geisler,Janos Demeter,Charles M. Perou,Per Eystein Lønning,Patrick O. Brown,Anne Lise Børresen-Dale,David Botstein +15 more
TL;DR: The results strongly support the idea that many of these breast tumor subtypes represent biologically distinct disease entities.
Journal ArticleDOI
Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer
Edward H. Romond,Edith A. Perez,John Bryant,Vera J. Suman,Charles E. Geyer,Nancy E. Davidson,Elizabeth Tan-Chiu,Silvana Martino,Soonmyung Paik,Peter A. Kaufman,Sandra M. Swain,Thomas M. Pisansky,Louis Fehrenbacher,Leila A. Kutteh,Victor G. Vogel,Daniel W. Visscher,Greg Yothers,Robert B. Jenkins,Ann M. Brown,S. R. Dakhil,Eleftherios P. Mamounas,Wilma L. Lingle,Pamela M. Klein,James N. Ingle,Norman Wolmark +24 more
TL;DR: Tastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer.
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