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Lysosomes and LAMPs as Autophagy Drivers of Drug Resistance in Colorectal Cancer

Tsvetomira Ivanova^1,2, Yordan Sbirkov^1,2, Maria Kazakova^1,2

¹Department of Medical Biology, Medical University-Plovdiv, 4000 Plovdiv, Bulgaria.

|April 25, 2025

Abstract:

Colorectal cancer (CRC) is among the most malignant pathologies worldwide. A major factor contributing to the poor prognosis of neoplastic diseases is the development of drug resistance. It significantly reduces the utility of most therapeutic protocols and necessitates the search for novel biomarkers and treatment strategies to combat cancer. An evolutionarily conserved catabolic mechanism, autophagy maintains nutrient recycling and metabolic adaptation and is also closely related to carcinogenesis, playing a dual role. Autophagy inhibition can limit the growth of tumors and improve the response to cancer therapeutics. Lysosomes, key players in autophagy, are also considered promising targets for anticancer treatment. There are still insufficient data on the role of poorly studied glycoproteins related to autophagy, such as the lysosome-associated membrane glycoproteins (LAMPs). They can act as multifunctional molecules involved in a multitude of processes like autophagy and cancer development. In the current review, we summarize the recent data on the double-faceted role of autophagy in cancer with a focus on drug resistance in CRC and on the roles of lysosomes and LAMPs in these interconnected processes. Several lysosomotropic drugs are discussed as options to overcome cancer cell chemoresistance. The complex networks that underline defined autophagic pathways in the context of CRC carcinogenesis and the role of autophagy, especially of LAMPs as drivers of drug resistance, are outlined.

Insights

Autophagy and its related molecules, like lysosome-associated membrane glycoproteins (LAMPs), play a dual role in colorectal cancer (CRC) and drug resistance. Targeting these pathways, especially lysosomes, offers new strategies to overcome chemoresistance in CRC.

Area of Science:

Oncology
Cell Biology
Molecular Medicine

Background:

Colorectal cancer (CRC) presents a significant global health challenge, with drug resistance severely limiting treatment efficacy.
Autophagy, a cellular recycling process, plays a complex, dual role in cancer development and progression.
Lysosomes and associated glycoproteins (LAMPs) are increasingly recognized for their involvement in cancer and autophagy.

Purpose of the Study:

To review the multifaceted role of autophagy in colorectal cancer (CRC) and its impact on drug resistance.
To highlight the specific involvement of lysosomes and LAMPs in CRC carcinogenesis and therapeutic resistance.
To discuss potential therapeutic strategies targeting autophagy and lysosomes to overcome chemoresistance.

Main Methods:

Literature review of recent research on autophagy, lysosomes, LAMPs, and CRC.
Analysis of the dual role of autophagy in cancer, focusing on drug resistance mechanisms.
Synthesis of data on lysosomal function and LAMPs in the context of CRC.

Main Results:

Autophagy exhibits a dual role in CRC, potentially promoting or inhibiting tumor growth and influencing drug response.
Lysosomes are critical components of autophagy and represent promising targets for anticancer therapies.
LAMPs are implicated as key regulators in autophagy-driven CRC progression and chemoresistance.

Conclusions:

Understanding the intricate role of autophagy, lysosomes, and LAMPs is crucial for developing effective CRC treatments.
Inhibition of autophagy and targeting lysosomes, particularly with lysosomotropic drugs, show promise in overcoming CRC chemoresistance.
LAMPs represent potential biomarkers and therapeutic targets for combating drug-resistant colorectal cancer.

Read full analysis

Keywords:

CRC LAMPs autophagy drug resistance lysosomes

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