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The Science of Cancer: Orchestrating a Holistic Approach to Drug Discovery

Publish Date

16 OCT 2023

Author

Paul Lyne

Overview

A one-size-fits all approach to cancer no longer suffices. Arriving at this understanding has been a transformative journey for the science of cancer.

All cancers are alike but they are alike in a unique way.

A one-size-fits all approach to cancer no longer suffices. Arriving at this understanding has been a transformative journey for the science of cancer. And, as we dive ever deeper into the intricate tapestry of cancer’s complexity, there is a sentiment that resonates deeply with me.

Cancer is a double-edged sword. On the one hand, it’s a substantial and meaningful disease that has a massive impact on society. On the other hand, it’s intellectually stimulating. Our current understanding of cancer is robust, yet so much remains undiscovered. Patients facing an uncertain future trust us to infuse hope into their lives through novel therapies crafted by my colleagues just a few floors below.

At Merck KGaA, Darmstadt, Germany, this duality defines our purpose and patient-focused approach. Conquering this mighty adversary calls for a unified interdisciplinary effort. We recognize that the answers do not lie in isolating a single mechanism, but in orchestrating insights from diverse fields. The science of drug discovery and development harmonizes biology, chemistry, pharmacokinetics, structural biology, devices and delivery systems, and more—a landscape of possibilities that fuels my passion.  

Our journey takes us deep into the “science of cancer.” In his book, The Emperor of All Maladies: A Biography of Cancer, Dr. Siddhartha Mukherjee astutely observes that the common thread uniting all cancers is the name itself. Yet within each diagnosis resides a complex blueprint interwoven by genetics, environment, treatment response, and an element of chance. Sounds much like what we use in drug discovery. Can we not then hold up a mirror to these intricacies and design treatments tailored to each individual’s unique needs?

Our new ‘game plan’ is a pragmatic, holistic approach that connects every research idea to a therapeutic mission. Every one of our endeavors must impact a patient’s journey, address an unmet need, and contribute to the collective progress in the fight against cancer.  

This plan underpins the evolution of our pipeline. Within our core areas of expertise, we’re forging convergence and focusing our efforts on antibody-drug conjugates (ADC), DNA damage response (DDR), tumor immunology (TI) and intrinsic tumor signaling.

What I’m really excited about right now are ADCs, first introduced 20 years ago (a monoclonal antibody connected to a cytotoxic payload by a chemical linker), but most associated with their own unique toxicities. Since then, we’ve been learning how to make these more tolerable and effective. Now, by also looking to modify the payload by using immune-stimulating agents, or in combination therapies with immunotherapies, we have the opportunity to create both a long-lasting response and, the potential of turning more cancer patients into cancer survivors.

Our gaze also focuses on DDR, which may be the Achilles heel for many cancers. This innovative approach sabotages a cancer cell’s ability to repair DNA damage and we have a strong DDR clinical profile supported by research, particularly in the area of synthetic lethality.
 
We are focused on developing the next generation of immune-oncology therapies, aiming to bring benefit to those patients that have relapsed from, or are refractory to checkpoint drugs.

As we further our efforts in oncogenic signaling, new horizons emerge. Tackling tumor intrinsic signaling redefines our arsenal against resistance and our best-in-class investigational portfolio steers our progress toward enhanced treatment outcomes for already validated mechanisms.

We stand at the threshold of a golden era of cancer therapies where our multidisciplinary approach is the hallmark of our new strategy. While each cancer is unique, we discover opportunity in this complexity—the opportunity to transform lives, by combining science and caring.   

US-NONO-00482 10/23