Related Experiment Video

Updated: Feb 1, 2026

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 26, 2014

24.0K

Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review

Siti Muhamad Nur Husna1, Hern-Tze Tina Tan1, Rohimah Mohamud1

  • 1Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

Therapeutic Advances in Medical Oncology
|December 14, 2018
PubMed

Insights

Small molecule inhibitors targeting cyclin-dependent kinase 4 and 6 (CDK4/6), poly (adenosine diphosphate-ribose) polymerase (PARP), and phosphoinositide 3-kinase (PI3K) show promise for breast cancer treatment. This review details eight SMIs, their clinical trials, and limitations to guide future breast cancer therapies.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Breast cancer remains a leading cause of cancer-related death in women globally.
  • Small molecule inhibitors (SMIs) represent a promising therapeutic strategy, with significant progress in clinical trials.
  • Key protein targets for SMIs in breast cancer include CDK4/6, PARP, and PI3K.

Purpose of the Study:

  • To review recently approved and novel SMIs targeting CDK4/6, PARP, and PI3K for breast cancer treatment.
  • To analyze the mechanisms of action, clinical trial data, and limitations of these inhibitors.
  • To inform future development of targeted therapies and treatment regimens for breast cancer patients.

Main Methods:

  • Literature review of approved and novel small molecule inhibitors.
  • Analysis of clinical trial outcomes and limitations for selected inhibitors.
  • Discussion of the molecular targets and mechanisms of action for each SMI.

Main Results:

  • Eight SMIs targeting CDK4/6 (palbociclib, ribociclib, abemaciclib), PARP (olaparib, veliparib, talazoparib), and PI3K (buparlisib, alpelisib) are discussed.
  • These inhibitors have shown varying degrees of success in clinical trials, with some approved for patient treatment.
  • Limitations and challenges associated with each inhibitor class are identified.

Conclusions:

  • SMIs targeting CDK4/6, PARP, and PI3K are vital in advancing breast cancer treatment.
  • Understanding the clinical trial data and limitations of current SMIs is crucial for optimizing future therapeutic strategies.
  • Further research and development are needed to overcome limitations and improve outcomes for breast cancer patients.
Keywords:
CDK4/6 inhibitorPARP inhibitorPI3K inhibitorbreast cancerobjective response rateprogression-free survival

More Related Videos

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model09:29

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

Published on: March 20, 2020

18.9K
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer07:45

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer

Published on: May 18, 2020

7.0K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.9K
Review and Preview01:10

Review and Preview

In statistics, several tools are used to interpret the data. Measures of central tendency represent the characteristics of the data, such as mean, median, and mode. Additionally, measures of variance like standard deviation and range are used to find the spread of data from the mean. Relative standing measures the distance between data locations. Commonly used measures of relative standings are percentile, z score, and quartiles.
Percentiles are a type of fractile that partition data into...
8.4K
Review and Preview01:13

Review and Preview

Data are individual items of information obtained from a population or sample. Data may be classified as qualitative (categorical), quantitative continuous, or quantitative discrete. Because it is not practical to measure the entire population in a study, researchers use samples to represent the population. A random sample is a representative group from the population chosen by using a method that gives each individual in the population an equal chance of being included in the sample. Random...
11.3K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.5K
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
669