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Castel P, Toska E, Zumsteg ZS, et al. Rationale-based therapeutic combinations with PI3K inhibitors in cancer treatment. Mol Cell Oncol. 2014;1(3):e963447doi: 10.4161/23723548.2014.963447.
Castel, P., Toska, E., Zumsteg, Z. S., Carmona, F. J., Elkabets, M., Bosch, A., & Scaltriti, M. (2014). Rationale-based therapeutic combinations with PI3K inhibitors in cancer treatment. Molecular & cellular oncology, 1(3), e963447. https://doi.org/10.4161/23723548.2014.963447
Castel, Pau, et al. "Rationale-based therapeutic combinations with PI3K inhibitors in cancer treatment." Molecular & cellular oncology vol. 1,3 (2014): e963447. doi: https://doi.org/10.4161/23723548.2014.963447
Castel P, Toska E, Zumsteg ZS, Carmona FJ, Elkabets M, Bosch A, Scaltriti M. Rationale-based therapeutic combinations with PI3K inhibitors in cancer treatment. Mol Cell Oncol. 2014 Oct 29;1(3):e963447. doi: 10.4161/23723548.2014.963447. eCollection 2014. PMID: 27308344; PMCID: PMC4904898.
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Mol Cell Oncol. 2014 Oct 29;1(3):e963447. doi: 10.4161/23723548.2014.963447. eCollection 2014.

Rationale-based therapeutic combinations with PI3K inhibitors in cancer treatment.

Molecular & cellular oncology

Pau Castel, Eneda Toska, Zachary S Zumsteg, F Javier Carmona, Moshe Elkabets, Ana Bosch, Maurizio Scaltriti

Affiliations

  1. Human Oncology & Pathogenesis Program (HOPP); Memorial Sloan Kettering Cancer Center ; New York, NY USA.

PMID: 27308344 PMCID: PMC4904898 DOI: 10.4161/23723548.2014.963447

Abstract

The PI3K/AKT/mTOR signaling is important for cell proliferation, survival, and metabolism. Hyperactivation of this pathway is one of the most common signaling abnormalities observed in cancer and a substantial effort has recently been made to develop molecules targeting this signaling cascade. However, it is becoming evident that PI3K inhibitors used as single agents do not elicit dramatic or durable responses. Given the numerous mechanisms mediating intrinsic and acquired resistance to these agents, hypothesis-based combinatorial strategies are probably needed to fully exploit their antitumor activity. In the first part of this review, we briefly dissect the PI3K/AKT/mTOR axis and list the most advanced compounds targeting different nodes of this cascade. The second part focuses on what we believe to be the most promising rationale-based therapeutic combinations with PI3K/AKT/mTOR inhibitors in solid tumors, with special emphasis on breast cancer.

Keywords: AKT; PIK3CA; PTEN; resistance; targeted therapy

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