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Published on: December 28, 2021
Cell death in cancer in the era of precision medicine
Giuseppe Raschellà1, Gerry Melino2,3, Alessandra Gambacurta2
1ENEA Research Center Casaccia, Laboratory of Biosafety and Risk Assessment, Via Anguillarese, 301, 00123, Rome, Italy. giuseppe.raschella@enea.it.
Abstract:
Tumors constitute a large class of diseases that affect different organs and cell lineages. The molecular characterization of cancers of a given type has revealed an extraordinary heterogeneity in terms of genetic alterations and DNA mutations; heterogeneity that is further highlighted by single-cell DNA sequencing of individual patients. To address these issues, drugs that specifically target genes or altered pathways in cancer cells are continuously developed. Indeed, the genetic fingerprint of individual tumors can direct the modern therapeutic approaches to selectively hit the tumor cells while sparing the healthy ones. In this context, the concept of precision medicine finds a vast field of application. In this review, we will briefly list some classes of target drugs (Bcl-2 family modulators, Tyrosine Kinase modulators, PARP inhibitors, and growth factors inhibitors) and discuss the application of immunotherapy in tumors (T cell-mediated immunotherapy and CAR-T cells) that in recent years has drastically changed the prognostic outlook of aggressive cancers. We will also consider how apoptosis could represent a primary end point in modern cancer therapy and how "classic" chemotherapeutic drugs that induce apoptosis are still utilized in therapeutic schedules that involve the use of target drugs or immunotherapy to optimize the antitumor response.
Insights
Precision medicine leverages tumor genetic profiles to develop targeted cancer therapies. This review covers targeted drugs, immunotherapies like CAR-T cells, and apoptosis induction for improved cancer treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Tumors exhibit significant molecular and genetic heterogeneity, even within the same cancer type.
- Single-cell DNA sequencing reveals intricate genetic alterations and mutations in individual tumors.
- This heterogeneity poses challenges for effective cancer treatment strategies.
Purpose of the Study:
- To review modern therapeutic approaches in oncology, focusing on precision medicine.
- To discuss targeted drug classes and the role of immunotherapy in cancer treatment.
- To explore apoptosis as a therapeutic endpoint and its integration with other treatment modalities.
Main Methods:
- Review of literature on targeted cancer therapies, including Bcl-2 family modulators, Tyrosine Kinase inhibitors, PARP inhibitors, and growth factor inhibitors.
- Discussion of immunotherapeutic strategies such as T cell-mediated immunotherapy and CAR-T cells.
- Analysis of the role of apoptosis induction in cancer therapy, including conventional chemotherapeutics.
Main Results:
- Targeted drugs and immunotherapies, including CAR-T cells, have significantly improved prognoses for aggressive cancers.
- Precision medicine, guided by tumor genetic fingerprints, enables selective targeting of cancer cells.
- Apoptosis remains a key endpoint, with conventional chemotherapy complementing targeted drugs and immunotherapy.
Conclusions:
- The integration of targeted therapies, immunotherapy, and apoptosis induction represents a paradigm shift in cancer treatment.
- Precision medicine offers a tailored approach to combat cancer heterogeneity.
- Optimizing antitumor responses requires strategic combinations of diverse therapeutic modalities.
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