The War on Cancer: A Report from the Front Lines

Melmed, Gavin M.

doi:10.1080/08998280.2006.11928194

Cited by 2 publications

(2 citation statements)

References 171 publications

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“…However, only the long isoform is phosphorylated by the activation of JAK2 since the tyrosine residues of the receptor susceptible to being phosphorylated in the terminal C portion of the PRLR are not present in the short isoform of the receptor ( 20 ). Therefore, PRL can activate or inhibit other pathways, such as MAPK and phosphatidylinositol 3 kinase (PI3K), without recruiting STAT proteins ( 21 , 26 , 27 ). In breast cancer cell-derived cell lines, PRL activates both Src family kinases and the JAK/STAT, as well as PI3K/Akt and MAPK signaling pathways.…”

Section: Mechanism Of Action Of Prl In Lactotrophsmentioning

confidence: 99%

Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?

Ferraris

2023

Front. Endocrinol.

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The hypothalamic neuroendocrine catecholamine dopamine regulates the lactotroph function, including prolactin (PRL) secretion, proliferation, and apoptosis. The treatment of PRL-secreting tumors, formerly known as prolactinomas, has relied mainly on this physiological characteristic, making dopamine agonists the first therapeutic alternative. Nevertheless, the group of patients that do not respond to this treatment has few therapeutical options. Prolactin is another physiological regulator of lactotroph function, acting as an autocrine/paracrine factor that controls PRL secretion and cellular turnover, inducing apoptosis and decreasing proliferation. Furthermore, the signaling pathways related to these effects, mainly JAK/STAT and PI3K/Akt, and MAPK, have been extensively studied in prolactinomas and other tumors as therapeutic targets. In the present work, the relationship between PRL pathophysiology and prolactinoma development is explored, aiming to comprehend the value of PRL and PRLR-associated pathways as exploratory fields alternative to dopamine-related approaches, which are worth physiological characteristics that might be impaired and can be potentially restored or upregulated to provide more options to the patients.

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Section: Mechanism Of Action Of Prl In Lactotrophsmentioning

confidence: 99%

Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?

Ferraris

2023

Front. Endocrinol.

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“…There will also be a challenge of ambition. “Wars on cancer” have come and gone, 36 – 38 often with mixed appraisals of their success, 39 and it is easy to dismiss undertakings of this magnitude as just “too complex” or “too challenging”. But activities such as the Cancer Research UK “Grand Challenges” demonstrate that, with the appropriate framework and mentality, ambitious challenges can be aggressively tackled, 40 and appropriately funded.…”

Section: An Ambitious Framework For Actionmentioning

confidence: 99%

Molecularly profiled trials: toward a framework of actions for the “nil actionables”

Jordan¹

2021

Br J Cancer

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The sequencing of tumour or blood samples is increasingly used to stratify patients into clinical trials of molecularly targeted agents, and this approach has frequently demonstrated clinical benefit for those who are deemed eligible. But what of those who have no clear and evident molecular driver? What of those deemed to have “nil actionable” mutations? How might we deliver better therapeutic opportunities for those left behind in the clamour toward stratified therapeutics? And what significant learnings lie hidden in the data we amass but do not interrogate and understand? This Perspective article suggests a holistic approach to the future treatment of such patients, and sets a framework through which significant additional patient benefit might be achieved. In order to deliver upon this framework, it encourages and invites the clinical community to engage more enthusiastically and share learnings with colleagues in the early drug discovery community, in order to deliver a step change in patient care.

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The War on Cancer: A Report from the Front Lines

Cited by 2 publications

References 171 publications

Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?

Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?

Molecularly profiled trials: toward a framework of actions for the “nil actionables”

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