Remember the phase 1 study, whereby radiation worked so wonderfully well - with the Kazia drug paxalisib.
Now in recent weeks, more high-level research has been released from premier study institutions, around the world - which serves and explains just how the combination works. This is compelling research - it is becoming apparent that the right PI3K AKT mTOR and radiation will have a major impact....... in prolonging life in a whole range of cancer types.
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Independant of what the company say - we have broad world leading research, that our drug paxalisib is in fact, the best in this class of drug (key drivers are it works, and safety profile)
It is beyond imagination - as to the value of a drug, right now... that so compliments radiation in cancer, around the world - but here you have genuine and thus far unambiguous research - and actual human study results, to support what has been said.
So 2 items of new research follows- (This new research below follows similiar findings published in April 2022 from Birmingham University and of course Memorial Sloan Ketting - where the human studies with paxalisib and radiation are taking place.
I am inclined to think now that paxalisib will indeed go and be used with radiation for up to 20 different types of cancer.
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PI3K/AKT/mTOR pathway, hypoxia, and glucose metabolism: Potential targets to overcome radioresistance in small cell lung cancer☆
Huan Deng,
Yamei Chen,
Peijing Li,
Qingqing Hang,
Peng Zhang,
Ming Chen [email protected], and
Ying Jin [email protected]Authors Info & Affiliations
Published Online: 8 December 2022
Abstract
Small cell lung cancer (SCLC) is a highly aggressive tumor type for which limited therapeutic progress has been made. Platinum-based chemotherapy with or without thoracic radiotherapy remains the backbone of treatment, but most patients with SCLC acquire therapeutic resistance. Given the need for more effective therapies, better elucidation of the molecular pathogenesis of SCLC is imperative.
The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is frequently activated in SCLC and strongly associated with resistance to ionizing radiation in many solid tumors. This pathway is an important regulator of cancer cell glucose metabolism, and its activation probably effects radioresistance by influencing bioenergetic processes in SCLC. Glucose metabolism has three main branches—aerobic glycolysis, oxidative phosphorylation, and the pentose phosphate pathway—involved in radioresistance. The interaction between the PI3K/AKT/mTOR pathway and glucose metabolism is largely mediated by hypoxia-inducible factor 1 (HIF-1) signaling. The PI3K/AKT/mTOR pathway also influences glucose metabolism through other mechanisms to participate in radioresistance, including inhibiting the ubiquitination of rate-limiting enzymes of the pentose phosphate pathway.
This review summarizes our understanding of links among the PI3K/AKT/mTOR pathway, hypoxia, and glucose metabolism in SCLC radioresistance and highlights promising research directions to promote cancer cell death and improve the clinical outcome of patients with this devastating diseases.
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Targeting PI3K/AKT/mTOR Signaling Pathway as a Radiosensitization in Head and Neck Squamous Cell Carcinomas
by
Yu-Chieh Su
1,2
,
Wei-Chang Lee
2,
Chih-Chun WangShyh-An Yehen-Hui Cheno-JDepartment of Medicine, School of Medicine, I-Shou University, Kaohsiung 840203, Taiwan
Int. J. Mol. Sci. 2022,
23(24), 15749;
https://doi.org/10.3390/ijms232415749
Received: 20 October 2022 / Revised: 24 November 2022 / Accepted: 8 December 2022 / Published: 12 December 2022
Globally, there are over half a million new patients with head and neck squamous cell carcinomas (HNSCC) every year. The current therapeutic approaches to HNSCC are surgery and adjuvant radiotherapy. These approaches carry a high incidence of metastasis or recurrence from HNSCC cells’ radioresistance. Recent studies have revealed that a combination with radiosensitizers can be used to improve the radioresistance in HNSCC; however, few agents are approved as radiosensitizers. The constitutive activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a vitally oncogenic type of signaling that promotes tumorigenesis, metastasis, and radiotherapy resistance in HNSCC. Pharmacological targeting of PI3K/AKT/mTOR signaling pathway is considered a promising strategy of radiosensitization in HNSCC. In this review, we summarize the oncogenic significance of PI3K/AKT/mTOR signaling in HNSCC with radiotherapy resistance and highlight the therapeutic potential of small molecule inhibitors against PI3K/AKT/mTOR signaling for the radiosensitization in HNSCC treatment. It provides a mechanistic framework for the development of new drugs for radiosensitization in HNSCC radiotherapy via targeting PI3K/AKT/mTOR signaling pathway.
Keywords:
head and neck cancer;
radiotherapy;
PI3K/AKT/mTOR;
radiosensitization
