Genomes and Genes
Affiliation: University of California
- Atefi M, Titz B, Avramis E, Ng C, Wong D, Lassen A, et al. Combination of pan-RAF and MEK inhibitors in NRAS mutant melanoma. Mol Cancer. 2015;14:27 pubmed publisher..The combination of PRiâ€‰+â€‰MEKi can be an effective regimen for blocking proliferation of NRAS mutant melanomas when there is higher activity of the MAPK pathway and dependence of proliferation and survival on this pathway. ..
- Eroglu Z, Kim D, Wang X, Camacho L, Chmielowski B, Seja E, et al. Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab. Eur J Cancer. 2015;51:2689-97 pubmed publisher..5 year survival rates of 16% (95% CI, 9-23%). CTLA-4 blockade with tremelimumab can lead to very long duration of objective anti-tumour responses beyond 12 years. ..
- ..Rationally combining targeted therapies to address the mechanism of resistance or combining BRAF inhibitors with other effective therapies such as immunotherapy may result in further improvement in outcomes for patients. ..
- Schadendorf D, Amonkar M, Stroyakovskiy D, Levchenko E, Gogas H, De Braud F, et al. Health-related quality of life impact in a randomised phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma. Eur J Cancer. 2015;51:833-40 pubmed publisher..Clinicaltrials.gov registration number: NCT01584648). ..
- Puzanov I, Amaravadi R, McArthur G, Flaherty K, Chapman P, Sosman J, et al. Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib: Patterns of disease progression and clinical management of limited progression. Eur J Cancer. 2015;51:1435-43 pubmed publisher..Some patients with melanoma achieved long-term survival with vemurafenib monotherapy. Continuation of vemurafenib after PD might be beneficial in some patients because remaining disease might continue to respond to BRAF inhibition. ..
- Hu Lieskovan S, Homet Moreno B, Ribas A. Excluding T Cells: Is Î²-Catenin the Full Story?. Cancer Cell. 2015;27:749-50 pubmed publisher..Further insights are needed into the mechanisms leading to a lack of T cell infiltration of cancers and primary immune resistance. ..
- Ribas A, Weber J, Chmielowski B, Comin Anduix B, Lu D, Douek M, et al. Intra-lymph node prime-boost vaccination against Melan A and tyrosinase for the treatment of metastatic melanoma: results of a phase 1 clinical trial. Clin Cancer Res. 2011;17:2987-96 pubmed publisher..These findings support further development of this investigational agent and the concept of therapeutic vaccination in metastatic melanoma. ..
- Kalbasi A, Ribas A. Antigen Presentation Keeps Trending in Immunotherapy Resistance. Clin Cancer Res. 2018;24:3239-3241 pubmed publisher..i>Clin Cancer Res; 24(14); 3239-41. ©2018 AACRSee related article by Huang et al., p. 3366. ..
- Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16:908-18 pubmed publisher..These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumab-refractory melanoma. Merck Sharp & Dohme. ..
- Ribas A. Adaptive Immune Resistance: How Cancer Protects from Immune Attack. Cancer Discov. 2015;5:915-9 pubmed publisher..Recognizing the specific adaptive resistance mechanisms in each case is likely to allow the personalized development of immunotherapies tailored to block how a particular cancer protects itself from the immune system. ..
- Hu Lieskovan S, Mok S, Homet Moreno B, Tsoi J, Robert L, Goedert L, et al. Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma. Sci Transl Med. 2015;7:279ra41 pubmed publisher..Our findings support the testing of triple combination therapy of BRAF and MEK inhibitors with immunotherapy in patients with BRAF(V600E) mutant metastatic melanoma. ..
- Ribas A, Camacho L, Lee S, Hersh E, Brown C, Richards J, et al. Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma. J Transl Med. 2010;8:89 pubmed publisher..The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma. NCT00107159. ..
- Ribas A, Hu Lieskovan S. What does PD-L1 positive or negative mean?. J Exp Med. 2016;213:2835-2840 pubmed..Finally, a tumor that is unable to express PD-L1 because of a genetic event will always be negative for PD-L1 on cancer cells. ..
- Shin D, Zaretsky J, Escuin Ordinas H, García Díaz A, Hu Lieskovan S, Kalbasi A, et al. Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations. Cancer Discov. 2017;7:188-201 pubmed publisher..Cancer Discov; 7(2); 188-201. ©2016 AACR.See related commentary by Marabelle et al., p. 128This article is highlighted in the In This Issue feature, p. 115. ..
- Schadendorf D, Dummer R, Hauschild A, Robert C, Hamid O, Daud A, et al. Health-related quality of life in the randomised KEYNOTE-002 study of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory melanoma. Eur J Cancer. 2016;67:46-54 pubmed publisher..HRQoL was better maintained with pembrolizumab than with chemotherapy in KEYNOTE-002, supporting the use of pembrolizumab in patients with ipilimumab-refractory melanoma. ..
- Shin D, Ribas A. The evolution of checkpoint blockade as a cancer therapy: what's here, what's next?. Curr Opin Immunol. 2015;33:23-35 pubmed publisher..Future studies will define bio-markers of these therapies and how to target them alone or in combination with other immunotherapies, chemotherapy, radiotherapy and small molecule inhibitors. ..
- Nowicki T, Akiyama R, Huang R, Shintaku I, Wang X, Tumeh P, et al. Infiltration of CD8 T Cells and Expression of PD-1 and PD-L1 in Synovial Sarcoma. Cancer Immunol Res. 2017;5:118-126 pubmed publisher..Cancer Immunol Res; 5(2); 118-26. Â©2016 AACR. ..
- Sharma P, Hu Lieskovan S, Wargo J, Ribas A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017;168:707-723 pubmed publisher..As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients. ..
- García Díaz A, Shin D, Moreno B, Saco J, Escuin Ordinas H, Rodriguez G, et al. Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression. Cell Rep. 2017;19:1189-1201 pubmed publisher..Therefore, these studies map the signaling pathway of interferon-gamma-inducible PD-1 ligand expression. ..
- Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka R, Michielin O, et al. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017;170:1109-1119.e10 pubmed publisher..These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. VIDEO ABSTRACT. ..
- Atefi M, Avramis E, Lassen A, Wong D, Robert L, Foulad D, et al. Effects of MAPK and PI3K pathways on PD-L1 expression in melanoma. Clin Cancer Res. 2014;20:3446-57 pubmed publisher..PD-L1-exposed lymphocytes decrease MAPK signaling, which is corrected by exposure to vemurafenib, providing potential benefits of combining this drug with immunotherapies. ..
- Lassen A, Atefi M, Robert L, Wong D, Cerniglia M, Comin Anduix B, et al. Effects of AKT inhibitor therapy in response and resistance to BRAF inhibition in melanoma. Mol Cancer. 2014;13:83 pubmed publisher..AKTi combined with BRAFi-based therapy may benefit patients with tumors harboring BRAF mutations and particularly PTEN deletions or AKT mutations. ..
- Ribas A, Kefford R, Marshall M, Punt C, Haanen J, Marmol M, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol. 2013;31:616-22 pubmed publisher..This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy...
- Ribas A, Wargo J, Comin Anduix B, Sanetti S, Schumacher L, McLean C, et al. Enhanced tumor responses to dendritic cells in the absence of CD8-positive cells. J Immunol. 2004;172:4762-9 pubmed..Elucidation of the signaling events that activate these effective cytotoxic cells and the putative suppressive mechanisms in a wild-type environment may provide means to enhance the clinical activity of DC-based approaches. ..