Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity
Over the last three decades, p21-activated kinases (PAKs) have emerged as prominent intracellular nodular signaling molecules in cancer cells with a spectrum of cancer-promoting functions ranging from cell survival to anchorage-independent growth to cellular invasiveness. As PAK family members are w...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/462 |
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| author | Deivendran Sankaran Revikumar Amjesh Aswathy Mary Paul Bijesh George Rajat Kala Sunil Saini Rakesh Kumar |
| author_facet | Deivendran Sankaran Revikumar Amjesh Aswathy Mary Paul Bijesh George Rajat Kala Sunil Saini Rakesh Kumar |
| author_sort | Deivendran Sankaran |
| collection | DOAJ |
| description | Over the last three decades, p21-activated kinases (PAKs) have emerged as prominent intracellular nodular signaling molecules in cancer cells with a spectrum of cancer-promoting functions ranging from cell survival to anchorage-independent growth to cellular invasiveness. As PAK family members are widely overexpressed and/or hyperactivated in a variety of human tumors, over the years PAKs have also emerged as therapeutic targets, resulting in the development of clinically relevant PAK inhibitors. Over the last two decades, this has been a promising area of active investigation for several academic and pharmaceutical groups. Similar to other kinases, blocking the activity of one PAK family member leads to compensatory activity on the part of other family members. Because PAKs are also activated by stress-causing anticancer drugs, PAKs are components in the rewiring of survival pathways in the action of several therapeutic agents; in turn, they contribute to the development of therapeutic resistance. This, in turn, creates an opportunity to co-target the PAKs to achieve a superior anticancer cellular effect. Here we discuss the role of PAKs and their effector pathways in the modulation of cellular susceptibility to cancer therapeutic agents and therapeutic resistance. |
| first_indexed | 2024-03-11T09:07:24Z |
| format | Article |
| id | doaj.art-d6a22b3a20e04272800b71e48c62aab9 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:07:24Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d6a22b3a20e04272800b71e48c62aab92023-11-16T19:18:35ZengMDPI AGBiomedicines2227-90592023-02-0111246210.3390/biomedicines11020462Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic SensitivityDeivendran Sankaran0Revikumar Amjesh1Aswathy Mary Paul2Bijesh George3Rajat Kala4Sunil Saini5Rakesh Kumar6Signal Transduction and Molecular Pharmacology, The Institute of Cancer Research, London SW7 3RP, UKCentre for Integrative Omics Data Science, Yenepoya (Deemed to be) University, Mangalore 578018, IndiaCancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, IndiaCancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, IndiaCancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun 248016, IndiaCancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun 248016, IndiaCancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun 248016, IndiaOver the last three decades, p21-activated kinases (PAKs) have emerged as prominent intracellular nodular signaling molecules in cancer cells with a spectrum of cancer-promoting functions ranging from cell survival to anchorage-independent growth to cellular invasiveness. As PAK family members are widely overexpressed and/or hyperactivated in a variety of human tumors, over the years PAKs have also emerged as therapeutic targets, resulting in the development of clinically relevant PAK inhibitors. Over the last two decades, this has been a promising area of active investigation for several academic and pharmaceutical groups. Similar to other kinases, blocking the activity of one PAK family member leads to compensatory activity on the part of other family members. Because PAKs are also activated by stress-causing anticancer drugs, PAKs are components in the rewiring of survival pathways in the action of several therapeutic agents; in turn, they contribute to the development of therapeutic resistance. This, in turn, creates an opportunity to co-target the PAKs to achieve a superior anticancer cellular effect. Here we discuss the role of PAKs and their effector pathways in the modulation of cellular susceptibility to cancer therapeutic agents and therapeutic resistance.https://www.mdpi.com/2227-9059/11/2/462PAKscancermetastasistherapeutic sensitivitycombination therapyclinical trials |
| spellingShingle | Deivendran Sankaran Revikumar Amjesh Aswathy Mary Paul Bijesh George Rajat Kala Sunil Saini Rakesh Kumar Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity Biomedicines PAKs cancer metastasis therapeutic sensitivity combination therapy clinical trials |
| title | Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity |
| title_full | Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity |
| title_fullStr | Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity |
| title_full_unstemmed | Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity |
| title_short | Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity |
| title_sort | hyperactivation of p21 activated kinases in human cancer and therapeutic sensitivity |
| topic | PAKs cancer metastasis therapeutic sensitivity combination therapy clinical trials |
| url | https://www.mdpi.com/2227-9059/11/2/462 |
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