Related Experiment Video

Updated: Jan 9, 2026

Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
09:45

Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines

Published on: August 21, 2019

7.4K

Lars2-signaling mediates platinum resistance by accumulating cancer stem cell population and suppressing anti-tumor

Yuqing Wang1, Min Deng1, Haipeng Lei1

  • 1Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China; Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China; Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China; Zhuhai UM Science & Technology Research Institute, Hengqin, China.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|December 4, 2025
PubMed

Insights

This study reveals LARS2 signaling as a key driver of platinum chemotherapy resistance in breast cancer. Inhibiting LARS2 signaling can overcome resistance and enhance immunotherapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Platinum-based chemotherapy is vital for cancer treatment but often fails due to acquired drug resistance.
  • Understanding novel resistance mechanisms is crucial for improving patient outcomes.

Purpose of the Study:

  • To elucidate a novel LARS2 signaling-mediated resistance mechanism in platinum-treated mammary tumors.
  • To explore therapeutic strategies to overcome platinum resistance and enhance immunotherapy.

Main Methods:

  • Multi-omics analyses in cancer patients and mouse models.
  • Functional validation of LARS2 signaling pathways.
  • Assessment of cancer stem cell enrichment and tumor microenvironment modulation.

Main Results:

  • Platinum treatment upregulates LARS2 via a danger-triggered response, increasing chromatin accessibility.
  • LARS2 signaling promotes resistance by enriching cancer stem cells and inducing TGF-β-mediated immunosuppression (M2 polarization, CD8+ T cell exhaustion).
  • Combination therapy of carboplatin with LARS2 inhibition reversed platinum resistance and restored PD-1 blockade sensitivity in preclinical models.

Conclusions:

  • LARS2 signaling represents a significant mechanism of platinum chemotherapy resistance.
  • Targeting LARS2 signaling offers a promising therapeutic strategy for overcoming resistance in breast cancer and other platinum-treated malignancies.
  • This approach can potentially re-sensitize tumors to immunotherapy.
Keywords:
Breast cancerCancer stem cellImmunosuppressionPlatinum resistance

More Related Videos

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

3.1K
Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

20.1K

Related Concept Videos

Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.8K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
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...
8.6K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K