José Baselga
Breast cancer oncologist who led the BOLERO-2 trial showing that the mTOR inhibitor everolimus added to hormone therapy lengthens progression-free survival
Deceased (1959–2021) · Executive Vice President, Oncology R&D, AstraZeneca (2019–2021) · Physician-in-Chief, Memorial Sloan Kettering Cancer Center · President, AACR (2015–2016) · Massachusetts General Hospital Cancer Center (affiliation on BAS2012, 2011)
Portrait: Wikimedia Commons
Breast cancers that depend on oestrogen are treated with hormone therapy, but many eventually stop responding. Laboratory work had linked this resistance to activation of the mTOR pathway. José Baselga led BOLERO-2, a phase 3 trial of 724 women, to test the idea: everolimus, an mTOR inhibitor, added to the hormone drug exemestane versus exemestane with a placebo.
At the interim analysis, median progression-free survival was 6.9 months with everolimus and 2.8 months with placebo as judged by local investigators, and 10.6 versus 4.1 months by central review. Side effects included mouth sores, anaemia and lung inflammation. The trial is one of the clearest tests in people that mTOR matters in a common cancer.
Baselga was born in Barcelona in 1959 and trained at Memorial Sloan Kettering, later led oncology at Vall d'Hebron in Barcelona and became Physician-in-Chief at Memorial Sloan Kettering. He took part in developing several breast cancer drugs, including trastuzumab, pertuzumab, alpelisib and everolimus, and was president of the American Association for Cancer Research in 2015–2016. He joined AstraZeneca in 2019 and died in March 2021.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2006 | M | mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt ORE2006 mTORC1 inhibition relieves feedback and activates upstream RTK-PI3K-Akt signalling. The Akt activation was demonstrated both in cancer cell lines and in patient tumours treated with RAD001 (everolimus), so this record carries a human pharmacodynamic component, not only in-vitro data. |
| 2008 | M | Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer CAR2008 mTORC1 inhibition activates the MAPK pathway via a PI3K-dependent feedback loop. Seen in tumour biopsies from patients with advanced solid tumours treated with RAD001 (everolimus), where the rise depended on the dosing schedule, and in a mouse prostate cancer model, xenografts and cell lines. |
| 2011 | M | mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling ROD2011 mTOR kinase inhibition triggers feedback-dependent biphasic AKT reactivation, informing resistance. |
| 2012 | H | Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer (BOLERO-2) BAS2012 First author of BOLERO-2, the phase 3 trial in which adding everolimus to exemestane improved progression-free survival in hormone-receptor-positive advanced breast cancer. |
| 2014 | H | Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2† PIC2014 Senior author of the final BOLERO-2 overall-survival report, in which adding everolimus to exemestane did not significantly lengthen overall survival (31.0 vs 26.6 months), although the progression-free survival gain held. |
Co-authors in the Atlas
People with a profile here who share at least one study with José Baselga.
- Gabriel N. Hortobagyi 2 shared studies Breast cancer physician-scientist and senior author of BOLERO-2, the phase 3 trial that showed adding the mTOR inhibitor everolimus improves outcomes in advanced hormone-receptor-positive breast cancer
- Martine J. Piccart 2 shared studies Breast cancer oncologist who co-founded the Breast International Group and has led or co-led major academic trials such as HERA, MINDACT and ALTTO.
- Neal Rosen 2 shared studies Showed that blocking mTORC1 releases a feedback brake on receptor tyrosine kinases and AKT, explaining how tumours escape mTOR and PI3K inhibitors and shaping how these drugs are combined in the clinic
- Arkaitz Carracedo Cancer biologist who, as first author in 2008, showed that blocking mTORC1 can switch on the MAPK pathway through a PI3K-dependent feedback loop.
- George Thomas Purified and cloned S6K1, the kinase that became the classic readout of mTORC1 activity. His lab later showed that mice lacking S6K1 resist diet-induced obesity, and that amino acids signal to mTORC1 through the lipid kinase hVps34 (GUL2008)
- Lewis C. Cantley Co-discovered PI3K, the pathway that feeds into mTOR from growth factors
- Pier Paolo Pandolfi Showed that ERK directly phosphorylates and inactivates TSC2, wiring Ras/MAPK signalling into mTORC1 control, and that blocking mTORC1 in patients' tumours triggers a feedback rise in MAPK signalling
- Sara C. Kozma Studies the S6K/mTOR pathway and how it controls cell growth, ribosome production, diabetes and cancer, including mTOR signalling in liver cancer.
- Vanessa S. Rodrik-Outmezguine Showed that tumours reactivate AKT after mTOR kinase inhibition, and that the third-generation inhibitor RapaLink-1 overcomes mTOR resistance mutations
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