The authors review the plethora of novel agents currently in development or recently approved for the treatment of patients with multiple myeloma. Naymagon L & Abdul-Hay M. J Hematol Oncol 2016; 9: 52. doi:10.1186/s13045-016-0282-1

Figure 2: Therapeutic targeting of the PI3K/AKT/mTOR pathway.

This may be due to reactivation of the MAPK pathway, persistent activation of receptor tyrosine kinase, increased activity of the phosphatidylinositol-3 kinase-AKT pathway, or other mechanisms to evade the effects of the inhibition of mutant BRAF and MEK. 21 Receptor tyrosine kinase inhibitors such as imatinib, although initially developed for other indications, also show benefit in KIT-mutated melanoma. 22 Clinical trials using various combinations of BRAF, MEK, ERK, phosphatidylinositol-3 kinase, AKT and mammalian target of rapamycin inhibitors are currently underway.

This paper reviews the role of BRCA proteins and poly(ADP-ribose) polymerase-1 (PARP1) inhibitors in ovarian cancer, with a summary of ongoing clinical studies with PARP inhibitors. Brit J Cancer  2016;115:1157–1173. doi:10.1038/bjc.2016.311

In this paper, key clinical trials of poly(ADP-ribose) polymerase (PARP) inhibitors are summarized, and the place of the PARP inhibitors in the treatment of ovarian cancer is explored, with a focus on the importance of testing for BRCA and other biomarkers. Nat Rev Clin Oncol  2017;14:284–296. doi:10.1038/nrclinonc.2016.191

This review summarizes data from key clinical trials of poly [ADP-ribose] polymerase inhibitors and discusses how to integrate these agents into the current treatment landscape of ovarian cancer.  Nat Rev Clin Oncol  2017;14: 284–296. doi:10.1038/nrclinonc.2016.191

Furthermore, combining tankyrase inhibitors with targeted agents, such as AKT and PI3K inhibitors, or chemotherapy was effective in preclinical models of colon cancer 126 .

Kinase inhibitors Kinase inhibitors have proven mostly ineffective against the ALL PDX panel, despite the aberrant activity of a number of key signaling pathways implicated in ALL.

Mammalian target of rapamycin is a serine/threonine kinase that is a downstream effector of the PI3K/AKT pathway.

MEK inhibitors.  

MEK–AKT-pathway inhibition.  

This mechanism of resistance has been documented in patients treated with mTOR inhibitors, whereas a feedback loop lead by mTORC2, has been observed that results in AKT activation owing to growth factor receptor phosphorylation (including IGF-1R), 79 providing the rationale to combine these agents with either IGF-1R 80  or PI3K 81  inhibitors.

Last, aspirin has been hypothesized to act synergistically with ornithine decarboxylase (ODC) inhibitors 145 .

There is already interest in therapeutic exploitation of such somatic mutations, with trials investigating the role of drugs targeting  BRAF ,  MTOR ,  MEK  and  AKT  in ovarian cancer.