Cell Cycle and Beyond: Exploiting New RB1 Controlled Mechanisms for Cancer Therapy

Erik S. Knudsen, Steven C. Pruitt, Pamela A. Hershberger, Agnieszka Witkiewicz, David W. Goodrich

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Recent studies highlight the importance of the RB1 tumor suppressor as a target for cancer therapy. Canonically, RB1 regulates cell cycle progression and represents the downstream target for cyclin-dependent kinase (CDK) 4/6 inhibitors that are in clinical use. However, newly discovered features of the RB1 pathway suggest new therapeutic strategies to counter resistance and improve precision medicine. These therapeutic strategies include deepening cell cycle exit with CDK4/6 inhibitor combinations, selectively targeting tumors that have lost RB1, and expanding therapeutic index by mitigating therapy-associated adverse effects. In addition, RB1 impacts immunological features of tumors and the microenvironment that can enhance sensitivity to immunotherapy. Lastly, RB1 specifies epigenetically determined cell lineage states that are disrupted during therapy resistance and could be re-installed through the direct use of epigenetic therapies. Thus, new opportunities are emerging to improve cancer therapy by exploiting the RB1 pathway.

Original languageEnglish (US)
JournalTrends in Cancer
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Cell Cycle
Neoplasms
Therapeutics
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase 4
Precision Medicine
Tumor Microenvironment
Cell Lineage
Epigenomics
Immunotherapy

Keywords

  • CDK4
  • cyclin
  • E2F
  • epigenetics
  • EZH2
  • immunotherapy
  • palbociclib
  • RB1
  • retinoblastoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cell Cycle and Beyond : Exploiting New RB1 Controlled Mechanisms for Cancer Therapy. / Knudsen, Erik S.; Pruitt, Steven C.; Hershberger, Pamela A.; Witkiewicz, Agnieszka; Goodrich, David W.

In: Trends in Cancer, 01.01.2019.

Research output: Contribution to journalReview article

Knudsen, Erik S. ; Pruitt, Steven C. ; Hershberger, Pamela A. ; Witkiewicz, Agnieszka ; Goodrich, David W. / Cell Cycle and Beyond : Exploiting New RB1 Controlled Mechanisms for Cancer Therapy. In: Trends in Cancer. 2019.
@article{616408d63732412cab6df4d96430e6ae,
title = "Cell Cycle and Beyond: Exploiting New RB1 Controlled Mechanisms for Cancer Therapy",
abstract = "Recent studies highlight the importance of the RB1 tumor suppressor as a target for cancer therapy. Canonically, RB1 regulates cell cycle progression and represents the downstream target for cyclin-dependent kinase (CDK) 4/6 inhibitors that are in clinical use. However, newly discovered features of the RB1 pathway suggest new therapeutic strategies to counter resistance and improve precision medicine. These therapeutic strategies include deepening cell cycle exit with CDK4/6 inhibitor combinations, selectively targeting tumors that have lost RB1, and expanding therapeutic index by mitigating therapy-associated adverse effects. In addition, RB1 impacts immunological features of tumors and the microenvironment that can enhance sensitivity to immunotherapy. Lastly, RB1 specifies epigenetically determined cell lineage states that are disrupted during therapy resistance and could be re-installed through the direct use of epigenetic therapies. Thus, new opportunities are emerging to improve cancer therapy by exploiting the RB1 pathway.",
keywords = "CDK4, cyclin, E2F, epigenetics, EZH2, immunotherapy, palbociclib, RB1, retinoblastoma",
author = "Knudsen, {Erik S.} and Pruitt, {Steven C.} and Hershberger, {Pamela A.} and Agnieszka Witkiewicz and Goodrich, {David W.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.trecan.2019.03.005",
language = "English (US)",
journal = "Trends in Cancer",
issn = "2405-8033",
publisher = "Cell Press",

}

TY - JOUR

T1 - Cell Cycle and Beyond

T2 - Exploiting New RB1 Controlled Mechanisms for Cancer Therapy

AU - Knudsen, Erik S.

AU - Pruitt, Steven C.

AU - Hershberger, Pamela A.

AU - Witkiewicz, Agnieszka

AU - Goodrich, David W.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Recent studies highlight the importance of the RB1 tumor suppressor as a target for cancer therapy. Canonically, RB1 regulates cell cycle progression and represents the downstream target for cyclin-dependent kinase (CDK) 4/6 inhibitors that are in clinical use. However, newly discovered features of the RB1 pathway suggest new therapeutic strategies to counter resistance and improve precision medicine. These therapeutic strategies include deepening cell cycle exit with CDK4/6 inhibitor combinations, selectively targeting tumors that have lost RB1, and expanding therapeutic index by mitigating therapy-associated adverse effects. In addition, RB1 impacts immunological features of tumors and the microenvironment that can enhance sensitivity to immunotherapy. Lastly, RB1 specifies epigenetically determined cell lineage states that are disrupted during therapy resistance and could be re-installed through the direct use of epigenetic therapies. Thus, new opportunities are emerging to improve cancer therapy by exploiting the RB1 pathway.

AB - Recent studies highlight the importance of the RB1 tumor suppressor as a target for cancer therapy. Canonically, RB1 regulates cell cycle progression and represents the downstream target for cyclin-dependent kinase (CDK) 4/6 inhibitors that are in clinical use. However, newly discovered features of the RB1 pathway suggest new therapeutic strategies to counter resistance and improve precision medicine. These therapeutic strategies include deepening cell cycle exit with CDK4/6 inhibitor combinations, selectively targeting tumors that have lost RB1, and expanding therapeutic index by mitigating therapy-associated adverse effects. In addition, RB1 impacts immunological features of tumors and the microenvironment that can enhance sensitivity to immunotherapy. Lastly, RB1 specifies epigenetically determined cell lineage states that are disrupted during therapy resistance and could be re-installed through the direct use of epigenetic therapies. Thus, new opportunities are emerging to improve cancer therapy by exploiting the RB1 pathway.

KW - CDK4

KW - cyclin

KW - E2F

KW - epigenetics

KW - EZH2

KW - immunotherapy

KW - palbociclib

KW - RB1

KW - retinoblastoma

UR - http://www.scopus.com/inward/record.url?scp=85064898568&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064898568&partnerID=8YFLogxK

U2 - 10.1016/j.trecan.2019.03.005

DO - 10.1016/j.trecan.2019.03.005

M3 - Review article

C2 - 31174843

AN - SCOPUS:85064898568

JO - Trends in Cancer

JF - Trends in Cancer

SN - 2405-8033

ER -